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Toggle navigation Topics by WorldWideScience.org Home About News Advanced Search Contact Us Site Map Help Sample records for acyclovir « 1 2 3 4 5 » 1. Acyclovir-induced thrombotic microangiopathy Science.gov (United States) Goli, R.; Mukku, K. K.; Devaraju, S. B. R.; Uppin, M. S. 2017-01-01 Acyclovir is a commonly used antiviral drug. Acute kidney injury (AKI) due to intratubular crystal precipitation and interstitial nephritis is well known. Here we present a case of acyclovir induced AKI in a 61 year old male with herpes zoster, which presented like thrombotic microangiopathy with acute interstitial nephritis. This is the first case report on acyclovir causing thrombotic microaniopathy with partial improvement in renal function after plasmapharesis. PMID:28356666 2. Managing recurrent genital herpes with acyclovir Directory of Open Access Journals (Sweden) Bedi T 1995-01-01 Full Text Available Seventy five patients of recurrent genital herpes (RGH treated with oral or topical acyclovir and placebo were compared and followed for periods ranging 4 to 8 years in a prospective study. Oral acyclovir definitely helps RGH patients; it shortens healing time; postpones recurrences and instills confidence in the patients. There is sufficient evidence that RGH dies a natural death with time as seen after 8 years follow up in placebo group patients. Topical use of acyclovir cream is not as useful as believed. 3. Acyclovir Science.gov (United States) ... such as amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), neomycin (Nes-RX, Neo-Fradin), paramomycin (Humatin), streptomycin, and tobramycin (Tobi, Nebcin); aspirin and other nonsteroidal ... 4. Topical delivery of acyclovir and ketoconazole. Science.gov (United States) Jacobs, Gerda A; Gerber, Minja; Malan, Maides M; du Preez, Jan L; Fox, Lizelle T; du Plessis, Jeanetta 2016-01-01 Viral and fungal cutaneous manifestations are regularly encountered in immunocompromised human immunodeficiency virus/acquired immunodeficiency syndrome individuals and can be treated by drugs such as acyclovir and ketoconazole, respectively. The aim of this study was to determine whether the novel Pheroid delivery system improved the transdermal delivery and/or dermal delivery of acyclovir and ketoconazole when incorporated into semi-solid formulations. Semi-solid products (creams and emulgels) containing these drug compounds were formulated, either with or without (control) the Pheroid delivery system. The stability of the formulated semi-solid products was examined over a period of six months and included the assay of the actives, pH, viscosity, mass loss and particle size observation. Vertical Franz cell diffusion studies and tape stripping methods were used to determine the in vitro, stratum corneum (SC)-epidermis and epidermis-dermis delivery of these formulations. Stability tests showed that none of the formulations were completely stable. Acyclovir showed a biphasic character during the in vitro skin diffusion studies for all the tested formulations. The Pheroidâ„¢ cream enhanced the transdermal, SC-epidermis and epidermis-dermis delivery of acyclovir the most. The average amount of ketoconazole diffused over 12 h showed improved delivery of ketoconazole, with the Pheroidâ„¢ emulgel exhibiting the best transdermal and epidermis-dermis delivery. The Pheroid formulae increased transdermal penetration as well as delivery to the dermal and epidermal skin layers. The Pheroid emulgel and the Pheroid cream increased the topical delivery of ketoconazole and acyclovir, respectively. 5. Acyclovir (Zovirax) pharmacokinetics in Quaker parakeets, Myiopsitta monachus. Science.gov (United States) Norton, T M; Kollias, G V; Clark, C H; Gaskin, J; Wilson, R C; Coniglario, J 1992-09-01 The pharmacokinetics of intravenous (i.v.) and intramuscular (i.m.) single-dose administration of acyclovir were determined in Quaker parakeets. After i.v. injection at a dose of 20 mg/kg of acyclovir, elimination half-life was estimated at 0.65 h, volume of distribution at steady state was 627.65 ml/kg, and clearance was 11.22 ml/kg/min. The estimated pharmacokinetic values after i.m. injection at a dose of 40 mg/kg of acyclovir were an elimination half-life of 0.71 h and a bioavailability of 90.1%. The peak plasma acyclovir concentration occurred at 15 min when the drug was administered i.m. Plasma concentrations of acyclovir were undetectable 4-6 h after i.v. administration and 6-8 h after i.m. administration. Oral (capsules) and intravenous (sodium salt) formulations of acyclovir were given by gavage at 80 mg/kg. Peak concentrations with the sodium salt formulation were lower and developed more slowly than with the capsules. In studies designed to detect excessive drug accumulation or adverse side effects, acyclovir was administered i.m. at 40 mg/kg every 8 h for 7 days. Plasma concentrations were determined 15 min after (peak) and just prior to drug administration (trough). In another study acyclovir was gavaged at a dose of 80 mg/kg every 8 h for 4 days. Acyclovir plasma concentrations were determined just prior to and 2 h after drug administration. In both experiments, the birds maintained normal appetite and weight and did not exhibit excessive drug accumulation. Acyclovir plasma concentrations ranging from 2.07 +/- 1.09 micrograms/ml to 3.93 +/- 1.13 micrograms/ml were maintained for 4 days when acyclovir was administered in the feed and water (sole source of food and water).(ABSTRACT TRUNCATED AT 250 WORDS) 6. Improving oral bioavailability of acyclovir using nanoparticulates of thiolated xyloglucan. Science.gov (United States) Madgulkar, Ashwini; Bhalekar, Mangesh R; Dikpati, Amrita A 2016-08-01 Acyclovir a BCS class III drug exhibits poor bioavailability due to limited permeability. The intention of this research work was to formulate and characterize thiolated xyloglucan polysaccharide nanoparticles (TH-NPs) of acyclovir with the purpose of increasing its oral bioavailability. Acyclovir-loaded TH-NPs were prepared using a cross-linking agent. Interactions of formulation excipients were reconnoitered using Fourier transform infrared spectroscopy (FT-IR). The formulated nanoparticles were lyophilised by the addition of a cryoprotectant and characterized for its particle size, morphology and stability and optimized using Box Behnken Design.The optimized TH-NP formulation exhibited particle size of 474.4±2.01 and an entrapment efficiency of 81.57%. A marked enhancement in the mucoadhesion was also observed. In-vivo study in a rat model proved that relative bioavailability of acyclovir TH-NPs is ∼2.575 fold greater than that of the marketed acyclovir drug suspension. 7. Colloidal dispersions for the delivery of acyclovir: A comparative study Directory of Open Access Journals (Sweden) Rita Cortesi 2011-01-01 Full Text Available This paper describes a comparative study on the performances of ethosomes and solid lipid nanoparticle as delivery systems for acyclovir. Ethosomes were spontaneously produced by dissolution of phosphatidylcholine and acyclovir in ethanol followed by addition of an aqueous buffer while solid lipid nanoparticle were produced by homogenization and ultrasonication. Both colloidal systems were morphologically characterized by cryo-transmission electron microscopy. The encapsulation efficiency was 94.2 ±2.8% for ethosomes and 53.2±0.2% for solid lipid nanoparticle. Concerning Z potential, both formulations are close to neutrality. The diffusion coefficients of the drug from ethosomes and solid lipid nanoparticle, determined by a Franz cell method, were 9.4 and 1.2-fold lower as compared to the free acyclovir in solution, thus evidencing the ability of both colloidal systems in enhancing the diffusion of the drug. The antiviral activity against HSV-1 of both systems was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that no significant differences in the antiviral activity were observed by acyclovir in the free or loaded forms. Taken together these results, colloidal systems could be interesting to mediate the penetration of acyclovir within Vero cells. 8. Colloidal Dispersions for the Delivery of Acyclovir: A Comparative Study Science.gov (United States) Cortesi, Rita; Ravani, Laura; Menegatti, Enea; Drechsler, M.; Esposito, Elisabetta 2011-01-01 This paper describes a comparative study on the performances of ethosomes and solid lipid nanoparticle as delivery systems for acyclovir. Ethosomes were spontaneously produced by dissolution of phosphatidylcholine and acyclovir in ethanol followed by addition of an aqueous buffer while solid lipid nanoparticle were produced by homogenization and ultrasonication. Both colloidal systems were morphologically characterized by cryo-transmission electron microscopy. The encapsulation efficiency was 94.2±2.8% for ethosomes and 53.2±0.2% for solid lipid nanoparticle. Concerning Z potential, both formulations are close to neutrality. The diffusion coefficients of the drug from ethosomes and solid lipid nanoparticle, determined by a Franz cell method, were 9.4 and 1.2-fold lower as compared to the free acyclovir in solution, thus evidencing the ability of both colloidal systems in enhancing the diffusion of the drug. The antiviral activity against HSV-1 of both systems was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that no significant differences in the antiviral activity were observed by acyclovir in the free or loaded forms. Taken together these results, colloidal systems could be interesting to mediate the penetration of acyclovir within Vero cells. PMID:23112407 9. Colloidal dispersions for the delivery of acyclovir: a comparative study. Science.gov (United States) Cortesi, Rita; Ravani, Laura; Menegatti, Enea; Drechsler, M; Esposito, Elisabetta 2011-11-01 This paper describes a comparative study on the performances of ethosomes and solid lipid nanoparticle as delivery systems for acyclovir. Ethosomes were spontaneously produced by dissolution of phosphatidylcholine and acyclovir in ethanol followed by addition of an aqueous buffer while solid lipid nanoparticle were produced by homogenization and ultrasonication. Both colloidal systems were morphologically characterized by cryo-transmission electron microscopy. The encapsulation efficiency was 94.2±2.8% for ethosomes and 53.2±0.2% for solid lipid nanoparticle. Concerning Z potential, both formulations are close to neutrality. The diffusion coefficients of the drug from ethosomes and solid lipid nanoparticle, determined by a Franz cell method, were 9.4 and 1.2-fold lower as compared to the free acyclovir in solution, thus evidencing the ability of both colloidal systems in enhancing the diffusion of the drug. The antiviral activity against HSV-1 of both systems was tested by plaque reduction assay in monolayer cultures of Vero cells. Data showed that no significant differences in the antiviral activity were observed by acyclovir in the free or loaded forms. Taken together these results, colloidal systems could be interesting to mediate the penetration of acyclovir within Vero cells. 10. Polymeric micelles for acyclovir drug delivery. Science.gov (United States) Sawdon, Alicia J; Peng, Ching-An 2014-10-01 Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of É›-caprolactone to form ACVpolycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were nontoxic. 11. Cocrystals of acyclovir with promising physicochemical properties. Science.gov (United States) Sarkar, Anindita; Rohani, Sohrab 2015-01-01 Cocrystal forming ability of antiviral drug acyclovir (ACV) with different coformers was studied. Three cocrystals containing ACV with fumaric acid, malonic acid, and DL-tartaric acid were isolated. Methods of cocrystallization included grinding with dropwise solvent addition and solvent evaporation. The cocrystals were characterized by powder X-ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. The crystal structure of the cocrystal with fumaric acid as conformer was determined by single crystal X-ray diffraction. Formation of supramolecular synthon was observed in the cocrystal. Stability with respect to relative humidity for the three cocrystals was evaluated. The aqueous solubility of the ACV-cocrystal materials was significantly improved with a maximum of malonic acid cocrystal, which was about six times more soluble at 35°C compared with that of parent ACV. The dissolution profile indicates that at any particular dissolution time, the concentration of cocrystals in the solution was higher than that of the parent ACV, and malonic acid cocrystals had a maximum release of about twice than the hydrated ACV. 12. Formulation and Optimization of Mucoadhesive Nanodrug Delivery System of Acyclovir OpenAIRE Bhosale, UV; Kusum, Devi V; Jain, N 2011-01-01 Acyclovir is an antiviral drug used for the treatment of herpes simplex virus infections, with an oral bioavailability of only 10–20% [limiting absorption in gastrointestinal tract to duodenum and jejunum] and half-life of about 3 h, and is soluble only at acidic pH (pKa 2.27). Mucoadhesive polymeric nanodrug delivery systems of acyclovir have been designed and optimized using 23 full factorial design. Poly (lactic-co-glycolic acid) (PLGA) (50:50) was used as the polymer along with polycarbop... 13. [Phosphoramidate derivatives of acyclovir--herpes virus replication inhibitors]. Science.gov (United States) Zakirova, N F; Shipitsyn, A V; Ias'ko, M V; Kochetkov, S N 2011-01-01 A number of new phosphoramidates of acyclovir--compounds of interest as anti-virals against resistant strains of virus herpes was synthesized. Several methods of synthesis of these compounds were suggested. Optimal method appeared to be the obtaining of phosphoramidates through the phosphomonocloride with its subsequent treatment with various amines. Two compounds have shown moderate activity against HSV-1. 14. Topical distribution of acyclovir in normal equine skin and equine sarcoids: An in vitro study. Science.gov (United States) Haspeslagh, M; Taevernier, L; Maes, A A; Vlaminck, L E M; De Spiegeleer, B; Croubels, S M; Martens, A M 2016-06-01 Topical acyclovir application is an owner-friendly treatment for occult equine sarcoids, without the caustic side-effects other topical treatments have. Variable clinical success rates have been described, but it is not known to what rate and extent acyclovir penetrates in and through equine skin from a topical formulation. In the current study, an in vitro Franz diffusion model was used to determine the permeation parameters for a generic 5% acyclovir cetomacrogol cream for both healthy and sarcoid equine skin. The distribution of acyclovir between different layers of both skin types was also evaluated. While acyclovir penetrated through both skin types, significantly less acyclovir permeated to the deep dermis of sarcoid skin (197.62ng/mm(3)) compared to normal skin (459.41ng/mm(3)). Within sarcoid skin samples, significantly higher acyclovir concentrations were found in the epidermis (983.59ng/mm(3)) compared to the superficial dermis (450.02ng/mm(3)) and the deep dermis. At each sample point, significantly more acyclovir permeated to the receptor fluid through normal skin compared to sarcoid skin, which is reflected in the significantly higher permeation parameters of normal skin. Normal skin was found to be more permissive for acyclovir, but even in sarcoid skin, enough acyclovir reached the deep dermis to treat a Herpes simplex virus infection. In the case of equine sarcoids, the treatment is aimed at the Bovine papillomavirus and no information is available on the susceptibility of the DNA polymerase of this virus for acyclovir. Therefore, further research is needed to determine the efficacy of acyclovir to treat equine sarcoids. 15. [Chickenpox case estimation in acyclovir pharmacy survey and early bioterrorism detection]. Science.gov (United States) Sugawara, Tamie; Ohkusa, Yasushi; Kawanohara, Hirokazu; Taniguchi, Kiyosu; Okabe, Nobuhiko 2011-11-01 Early potential health hazards and bioterrorism threats require early detection. Smallpox cases caused by terrorist could, for example, be treated by prescribing acyclovir to those having fever and vesicle exanthema diagnosed as chicken pox. We have constructed real-time pharmacy surveillance scenarios using information technology (IT) to monitor acyclovir prescription. We collected the number of acyclovir prescriptions from 5138 pharmacies using the Application Server Provider System (ASP) to estimate the number of cases. We then compared the number of those given acyclovir under 15 years old from pharmacy surveillance and sentinel surveillance for chickenpox under the Infection Disease Control Law. The estimated number of under 15 years old prescribed acyclovir in pharmacy surveillance resembled sentinel surveillance results and showed a similar seasonal chickenpox pattern. The correlation coefficient was 0.8575. The estimated numbers of adults, older than 15 but under 65 years old, and elderly, older than 65, prescribed acyclovir showed no clear seasonal pattern. Pharmacy surveillance for acyclovir identified the baseline and can be used to detect unusual chickenpox outbreak. Bioterrorism attack could potentially be detected using smallpox virus when acyclovir prescription for adults suddenly increases without outbreaks in children or the elderly. This acyclovir prescription monitoring such as an application is, to our knowledge, the first of its kind anywhre. 16. Alopecia following oral acyclovir for the treatment of herpes simplex keratitis. Science.gov (United States) Sharma, Ashok; Mohan, Kanwar; Sharma, Rajan; Nirankari, Verinder S 2014-01-01 The authors report acyclovir-induced alopecia in a patient treated for herpetic keratouveitis. A 32-years-old female was diagnosed with herpetic keratouveitis. She was placed on prednisolone acetate (1%) suspension four times a day, atropine sulfate (1%) thrice a day, and oral acyclovir 400 mg twice-daily. Three weeks following oral acylovir, keratouveitis improved, but she developed alopecia without any drug eruptions. Oral acyclovir was discontinued. Three months later, alopecia completely resolved. Alopecia may be considered a possible complication following oral acyclovir. 17. Alopecia following oral acyclovir for the treatment of herpes simplex keratitis Directory of Open Access Journals (Sweden) Ashok Sharma 2014-01-01 Full Text Available The authors report acyclovir-induced alopecia in a patient treated for herpetic keratouveitis. A 32-years-old female was diagnosed with herpetic keratouveitis. She was placed on prednisolone acetate (1% suspension four times a day, atropine sulfate (1% thrice a day, and oral acyclovir 400 mg twice-daily. Three weeks following oral acylovir, keratouveitis improved, but she developed alopecia without any drug eruptions. Oral acyclovir was discontinued. Three months later, alopecia completely resolved. Alopecia may be considered a possible complication following oral acyclovir. 18. Acyclovir in the prevention of duodenal ulcer recurrence DEFF Research Database (Denmark) Rune, S J; Linde, J; Bonnevie, O; 1990-01-01 This study tests the hypothesis that reactivation of a latent herpes simplex virus infection may be a cause of recurrent duodenal ulceration. Patients with recently healed duodenal ulcer were entered into a double blind, randomised study of maintenance treatment with the antiviral drug acyclovir...... (400 mg bid) versus placebo, to determine if suppression of herpes virus infection would influence the natural history of the ulcer disease. One hundred and fifteen patients entered the trial and 76 patients completed it according to the protocol. Endoscopy was performed when ulcer symptoms recurred...... and at the end of the 25 week trial period. In the acyclovir group the cumulated relapse rate was 63% compared with 56% in the placebo group (NS). This result suggests that reactivation of herpes simplex virus is not a cause of recurrent duodenal ulcer.... 19. Synthesis and characterization of novel dipeptide ester prodrugs of acyclovir Science.gov (United States) Nashed, Yasser E.; Mitra, Ashim K. 2003-07-01 Four dipeptide (Gly-Gly, Gly-Val, Val-Val, Val-Gly) ester prodrugs of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir, ACV) were synthesized. LC/MS was used to characterize the new prodrugs. Both 1H NMR and 13C NMR spectra of the four prodrugs of ACV were measured and assigned based on spectral comparison with compounds of similar structures. 20. Formulation and evaluation of acyclovir microcapsules using bakers yeast Institute of Scientific and Technical Information of China (English) Krishnan PN; Saraswathi R; Dilip C; Ramarao N 2010-01-01 Objective:To formulate and evaluate acyclovir microcapsules using bakers yeast. Methods:Acyclovir, pretreated yeast and deionised water were taken at a volumetric ratio of 1:2:4 respectively. This suspension was agitated in a magnetic stirrer at 25℃, 30℃, 35℃, and 40℃for 4 hours. The suspension was then centrifuged for 10 minutes at 2 000 rpm. The supernatant solution was decanted and the cells were washed 5 times with deionised water. Then the suspended drug entrapped yeast cells were dried in a lyophillizer for 48 hours. The yield was noted. Results:The first four formulations were done with 200 mg of the drug, followed by 400 mg for the next four formulations and 800 mg the last four formulations. SEM showed that the surface of the microcapsules was intact, with no burst characteristics. FTIR showed no interaction between acyclovir and the cell wall. DSC showed that the peak was within the standard values. The mean particle size for all the samples was 8 μm in diameter. The dissolution studies were done for all the twelve samples

and showed a Fickian model of diffusion. Conclusions:From the results it is inferred that the samples prepared at 40℃(FY-4, FY-8, FY-12) show better entrapment and release. So these samples are formulated in the form of a suspension and compared with marketed acyclovir suspension using HPLC technique. The formulated suspensions with FY-4, FY-8 and FY-12 shows drug content in accordance with the standards of the pharmacopoeial limits. « 1 2 3 4 5 » « 1 2 3 4 5 » 21. Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir. Science.gov (United States) Gupta, Swati; Agarwal, Abhinav; Gupta, Nishant Kumar; Saraogi, Gauravkant; Agrawal, Himanshu; Agrawal, G P 2013-12-01 The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders. 22. Design of Nanoparticles Loaded Acyclovir for Controlled Delivery System Directory of Open Access Journals (Sweden) Shadab Shahsavari 2015-10-01 Full Text Available Introduction: The aim of this research was to develop a new drug release systems based on Nanoparticles. In this study, the natural polymer chitosan was used for preparation of nanoparticles due to its unique properties, such as biocompatibility and biodegradability. Methods: The polymeric nano-drug controlled release system has been designed with experimental design D-optimal response surface methodology, for varied variables such as the concentration of acyclovir, concentration ratio of chitosan/ TPP and pH using the ionic gelation method. The nanoparticles were characterized morphologically by scanning electron microcopy (SEM, particle size analyser (DLS for determining size, zeta and PdI, Fourier Transform Infra-Red (FTIR Spectroscopy for determination of structure of nanoparticlesand thermo gravimetric analysis (TGAfor studying thermal behavior. The optimized nanoparticles were characterized. Results: The size of the particles was detected to be 132±24.3 nm; zeta potential was 32±2.87 mV; PdI of particles was 0.159 ±0.05; and calculated EE% was 85±4.38%. An in-vitro release study of the prepared nanoparticles illustrated that the percentage of acyclovir released from the nanoparticles was 80.17±2.45% within 48 hrs. Conclusion: The optimized nanoparticles according to SEM image, exhibited segregated and non-aggregated nanoparticles with sub-spherical smooth morphology and also the high thermal stability of acyclovir nanoparticles at temperature up to 200°C due to TGA analysis, which indicated a well-established structure of nanoparticles. 23. Attachment and penetration of acyclovir-resistant herpes simplex virus are inhibited by Melissa officinalis extract. Science.gov (United States) Astani, Akram; Navid, Mojdeh Heidary; Schnitzler, Paul 2014-10-01 Medicinal plants are increasingly of interest as novel source of drugs for antiherpetic agents, because herpes simplex virus (HSV) might develop resistance to commonly used antiviral drugs. An aqueous extract of Melissa officinalis and the phenolic compounds caffeic acid, p-coumaric acid and rosmarinic acid were examined for their antiviral activity against herpes simplex virus type 1 (HSV-1) acyclovir-sensitive and clinical isolates of acyclovir-resistant strains in vitro. When drugs were added during the intracellular replication of HSV-1 infected cells, no antiviral effect was observed by plaque reduction assay. However, Melissa extract interacted directly with free viral particles of two acyclovir-resistant HSV strains at low IC50 values of 0.13 and 0.23 µg/mL and high selectivity indices of 2692 and 1522, respectively. The Melissa extract and rosmarinic acid inhibited HSV-1 attachment to host cells in a dose-dependent manner for acyclovir-sensitive and acyclovir-resistant strains. These results indicate that mainly rosmarinic acid contributed to the antiviral activity of Melissa extract. Penetration of herpes viruses into cells was inhibited by Melissa extract at 80% and 96% for drug-sensitive and drug-resistant viruses, respectively. Melissa extract exhibits low toxicity and affects attachment and penetration of acyclovir-sensitive and acyclovir-resistant HSVs in vitro. Copyright © 2014 John Wiley & Sons, Ltd. 24. Controlled delivery of acyclovir from porous silicon micro- and nanoparticles Energy Technology Data Exchange (ETDEWEB) Maniya, Nalin H.; Patel, Sanjaykumar R.; Murthy, Z.V.P., E-mail: [email protected] 2015-03-01 Graphical abstract: - Highlights: • Porous silicon (PSi) was fabricated by electrochemical etching process. • Micro- and nanoparticles were prepared by ultrasonic fracture of PSi films. • Acyclovir was loaded into native, oxidized, and hydrosilylated PSi particles. • Micro- and nanoparticles displays controlled release behaviour for several days. • Drug release behaviour and release kinetics from PSi particles were studied. - Abstract: In this work, micro- and nanoparticles of porous silicon (PSi) are demonstrated to act as effective carrier for the controlled delivery of acyclovir (ACV). PSi films prepared by electrochemical etching were fractured by ultrasonication to prepare micro- and nanoparticles. PSi native particles were thermally oxidized (TOPSi) and thermally hydrosilylated using undecylenic acid (UnPSi). PSi particles with three different surface chemistries were then loaded with ACV by physical adsorption and covalent attachment. Such particles were characterized by scanning electron microscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. In vitro ACV release experiments in phosphate buffered saline showed sustained release behaviour from both micro- and nanoparticles and order of release was found to be native PSi > TOPSi > UnPSi. Drug release kinetics study using Korsmeyer-Peppas model suggested a combination of both drug diffusion and Si scaffold erosion based drug release mechanisms. 25. Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir. OpenAIRE Spruance, S. L.; Crumpacker, C S; Schnipper, L E; Kern, E. R.; Marlowe, S; Arndt, K A; Overall, J C 1984-01-01 To determine whether topical acyclovir in polyethylene glycol could reduce the severity of herpes simplex labialis if applied immediately after onset of a recurrence, 10% acyclovir in polyethylene glycol ointment or polyethylene glycol alone was prospectively dispensed to 352 patients in a double-blind, randomized trial. Sixty-nine subjects initiated treatment in the prodrome (57%) or erythema (43%) stage and were followed by clinical and virological criteria. The healing time (6.0 days), max... 26. Controlled delivery of acyclovir from porous silicon micro- and nanoparticles Science.gov (United States) Maniya, Nalin H.; Patel, Sanjaykumar R.; Murthy, Z. V. P. 2015-03-01 In this work, micro- and nanoparticles of porous silicon (PSi) are demonstrated to act as effective carrier for the controlled delivery of acyclovir (ACV). PSi films prepared by electrochemical etching were fractured by ultrasonication to prepare micro- and nanoparticles. PSi native particles were thermally oxidized (TOPSi) and thermally hydrosilylated using undecylenic acid (UnPSi). PSi particles with three different surface chemistries were then loaded with ACV by physical adsorption and covalent attachment. Such particles were characterized by scanning electron microscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. In vitro ACV release experiments in phosphate buffered saline showed sustained release behaviour from both micro- and nanoparticles and order of release was found to be native PSi > TOPSi > UnPSi. Drug release kinetics study using Korsmeyer-Peppas model suggested a combination of both drug diffusion and Si scaffold erosion based drug release mechanisms. 27. Preparation and evaluation of gastroretentive floating tablets of acyclovir. Science.gov (United States) Garg, Rajeev; Gupta, G D 2009-10-01 The present study performed by preparation and evaluation of floating tablets of Acyclovir as model drug for prolongation of gastric residence time. Floating effervescent tablets were formulated by various materials like hydroxypropyl methylcellulose K 4M, K 15M, psyllium husk, swelling agent as crospovidone and microcrystalline cellulose and gas generating agent like sodium bicarbonate and citric acid and evaluated for floating properties, swelling characteristics and in vitro drug release studies. Floating noneffervescent tablets were prepared by polypropylene foam powder and different matrix forming polymers like HPMC K 4M, Carbopol 934P, xanthan gum and sodium alginate. In vitro drug release studies were performed and drug release kinetics evaluated using the linear regression method was found to follow both the Higuchi and the Korsmeyer and Peppas equation. The drug release mechanism was found fickian type in most of the formulations. 28. Encapsulation of Acyclovir in new carboxylated cyclodextrin-based nanosponges improves the agent's antiviral efficacy. Science.gov (United States) Lembo, David; Swaminathan, Shankar; Donalisio, Manuela; Civra, Andrea; Pastero, Linda; Aquilano, Dino; Vavia, Pradeep; Trotta, Francesco; Cavalli, Roberta 2013-02-25 Cyclodextrin-based nanosponges (NS) are solid nanoparticles, obtained from the cross-linking of cyclodextrins that have been proposed as delivery systems for many types of drugs. Various NS derivatives are currently under investigation in order that their properties might be tuned for different applications. In this work, new carboxylated cyclodextrin-based nanosponges (Carb-NS) carrying carboxylic groups within their structure were purposely designed as novel Acyclovir carriers. TEM measurements revealed their spherical shape and size of about 400 nm. The behaviour of Carb-NS, with respect to the incorporation and delivery of Acyclovir, was compared to that of NS, previously investigated as a drug carrier. DSC, XRPD and FTIR analyses were used to investigate the two NS formulations. The results confirm the incorporation of the drug into the NS structure and NS-Acyclovir interactions. The Acyclovir loading into Carb-NS was higher than that obtained using NS, reaching about 70% (w/w). In vitro release studies showed the release kinetics of Acyclovir from Carb-NS to be prolonged in comparison with those observed with NS, with no initial burst effect. The NS uptake into cells was evaluated using fluorescent Carb-NS and revealed the nanoparticle internalisation. Enhanced antiviral activity against a clinical isolate of HSV-1 was obtained using Acyclovir loaded in Carb-NS. 29. Comparative study of effectiveness of oral acyclovir with oral erythromycin in the treatment of Pityriasis rosea. Science.gov (United States) Amatya, A; Rajouria, E A; Karn, D K 2012-01-01 Pityriasis rosea is an acute, self-limiting disease, probably infective in origin, affecting mainly children and young adults, characterized by distinctive skin eruptions and minimal constitutional symptoms. Both oral Erythromycin and oral Acyclovir have been used in its management. To compare the effectiveness of oral Erythromycin and oral Acyclovir in the treatment of Pityriasis rosea. Forty two patients with clinical diagnosis of Pityriasis rosea were enrolled. They were randomized into two groups. One group was given high-dose oral Acyclovir and another group oral Erythromycin in standard dose. The participants were evaluated one, two, four, six and eight weeks and six months after commencement of the study. Forty two patients including 26 males and 16 females completed the study. After 8th week, all patients showed complete response in both the groups. The response to oral Acyclovir compared with that to oral Erythromycin was better and was statistically significant in 1st, 2nd, 4th and 6th weeks. Although it is a self-limiting disease which resolves within three weeks to three months, this study reveals that both oral Acyclovir and oral Erythromycin are helpful in decreasing the severity and duration of Pityriasis rosea. Moreover, the study also indicates that oral Acyclovir is more effective than oral Erythromycin in reducing the severity and duration of Pityriasis rosea. 30. The effects of oral Acyclovir in the treatment of necrotizing Herpetic keratouveitis Directory of Open Access Journals (Sweden) "Hosseini Tehrani M;Poormostadam B;Vallaei N;Raiszadeh F " 2000-08-01 Full Text Available This study was conducted to evaluate the effects of administering oral acyclovir in conjunction with topical acyclovir and steroids in the treatment of necrotizing herpetic keratouveitis. All patients with necrotizing herpetic keratouveits who have been consulted during 1996-1997 at the farbi Eye Hospital were studied . the patients were randomly assigned to two groups. In the first group, topical acyclovir ointment and topical steroids were administered, while the second group took oral acyclovir, 1600 mg in four divided does in addition to the above mentioned treatment. The patients undervent follow-up examination every three days in the first three weeks and therafter periodically for one year.After three weeks, 92% and 88% improvement was observed in the first and second groups, respectively. The observed difference was not statistically significant. Making nonpharmacologic interventions such as application of soft contact lenses, corneal grafts, and conjunctival flaps were inevitable in some cases in both groups. Secondary infection was observed in three patients (first grop and two patients (2 and group.The sample size was not large enough to draw a definite statistical conclusion, but it seems that the addition of oral acyclovir has no added effect in the treatment of necrotizing herpetic keratouveitis than topical acyclovir and steroids. In this study , the males were affected more frequently than females. 31. Ocular sustained release nanoparticles containing stereoisomeric dipeptide prodrugs of acyclovir. Science.gov (United States) Jwala, Jwala; Boddu, Sai H S; Shah, Sujay; Sirimulla, Suman; Pal, Dhananjay; Mitra, Ashim K 2011-04-01 The objective of this study was to develop and characterize polymeric nanoparticles of appropriate stereoisomeric dipeptide prodrugs of acyclovir (L-valine-L-valine-ACV, L-valineD-valine-ACV, D-valine-L-valine-ACV, and D-valine-D-valine-ACV) for the treatment of ocular herpes keratitis. Stereoisomeric dipeptide prodrugs of acyclovir (ACV) were screened for bioreversion in various ocular tissues, cell proliferation, and uptake across the rabbit primary corneal epithelial cell line. Docking studies were carried out to examine the affinity of prodrugs to the peptide transporter protein. Prodrugs with optimum characteristics were selected for the preparation of nanoparticles using various grades of poly (lactic-coglycolic acid) (PLGA). Nanoparticles were characterized for the entrapment efficiency, surface morphology, size distribution, and in vitro release. Further, the effect of thermosensitive gels on the release of prodrugs from nanoparticles was also studied. L-valine-L-valine-ACV and L-valine-D-valine-ACV were considered to be optimum in terms of enzymatic stability, uptake, and cytotoxicity. Docking results indicated that L-valine in the terminal position increases the affinity of the prodrugs to the peptide transporter protein. Entrapment efficiency values of L-valine-L-valine-ACV and L-valine-D-valine-ACV were found to be optimal with PLGA 75:25 and PLGA 65:35 polymers, respectively. In vitro release of prodrugs from nanoparticles exhibited a biphasic release behavior with initial burst phase followed by sustained release. Dispersion of nanoparticles in thermosensitive gels completely eliminated the burst release phase. Novel nanoparticulate systems of dipeptide prodrugs of ACV suspended in thermosensitive gels may provide sustained delivery after topical administration. 32. [Delirium during oral therapy of herpes zoster with acyclovir. Case report and brief review of central nervous system side-effects of acyclovir]. Science.gov (United States) Braun, J S; Apel, I; Schäffer, S; Schumacher, M; Berger, M 1998-11-01 In differential diagnosis of a delir also adverse effects of medicaments have to be taken into account beside other causes. We report a case of an agitated delir with nocturnal disturbance of consciousness, confusion, restlessness and sleeplessness. This delir existed exclusively during the therapy of a cutaneous herpes zoster with zovirax-pills which can only be explained by a causal connection--after exclusion of other causes. As a so far undescribed predisposition for neurotoxicity of oral therapy with acyclovir signs of vascular encephalopathy were found in the patient's cranial magnetic resonance imaging. The central nervous side effects of acyclovir were summarized shortly. 33. Acyclovir-resistant herpetic keratitis in a solid-organ transplant recipient on systemic immunosuppression Directory of Open Access Journals (Sweden) Turner LD 2013-01-01 Full Text Available Liam Daniel Turner,1 Peter Beckingsale1,2,31Princess Alexandra Hospital; 2Terrace Eye Centre; 3Laser Sight, Brisbane, Queensland, AustraliaPurpose: To report a case of acyclovir-resistant herpetic keratitis in a solid-organ lung transplant recipient that was effectively treated with topical trifluridine.Methods: A case of a 35-year-old female with herpetic epithelial keratitis resistant to acyclovir is described. The patient presented following treatment for 4 weeks with topical acyclovir ointment five times per day and oral valacyclovir 1 g three times per day for herpetic keratitis with no resolution of the epithelial defect or symptoms. Corneal scrapes and swabs were taken for confirmation of the diagnosis and resistance testing. The results were positive for herpes simplex virus 1 and showed acyclovir resistance (inhibitor concentration 90 = 200 µg/mL and foscarnet sensitivity (inhibitor concentration 90 = 200 µg/mL. The patient was treated with topical trifluridine 2-hourly for 3 weeks and weaned off the drops over the following week.Results: The patient showed resolution of the epithelial defect, but did have significant corneal toxicity associated with the use of the trifluridine. At 8 weeks, the patient had some stromal shadowing associated with the recent active infection, but symptoms had settled.Conclusion: This case documents the effective use of topical trifluridine in proven acyclovir-resistant herpetic keratitis. It highlights three things: (1 the importance of considering topical trifluridine as an alternative to topical acyclovir in unresponsive disease; (2 the need to consider solid-organ transplant recipients in the immunocompromised population with resistant herpetic disease, and (3 the need to look for alternatives to treatment of resistant herpetic disease.Keywords: acyclovir resistance, herpetic keratitis, trifluridine 34. [Acyclovir may modulate clonal expansion of cd8+ lymphocytes induced by the Cytomegalovirus antigen]. Science.gov (United States) Gavilán, F; Caballero, J; Cárdenas, M; Moreno, J; MartÃnez, L; Gallego, C; Sánchez-Guijo, P; Torre-Cisneros, J 1999-10-01 Although the potent antiviral effect of acyclovir on the Herpes-simplex (HSV) and Varicela-zoster (VZV) virus and the scarce effectiveness versus Cytomegalovirus (CMV) is known, some data suggest that it may have an immunodulator implicated in the control of these viral disease. The aim of this study was to characterize this possible effect of acyclovir versus the CMV antigen. We stimulated cultures of mononuclear cells obtained in 7 healthy patients who were seropositive for CMV and HSV with CMV antigen, HSV and with phitohemaglutinine (PHA). The proliferation index and culture cell phenotype were later determined in the absence and presence of acyclovir (2 micrograms/ml). In another group the proliferation index and cell phenotype following stimulation with the CMV antigen were studied prior to and after treating the same volunteers with acyclovir for one week (800 mg/6h). The CMV antigen and HSV induced T cell proliferation predominantly involving the CD8+ subpopulation leading to an inversion of the CD4/CD8 quotient. On addition of acyclovir to the cell culture a moderate reduction was produced in lymphoproliferative response versus the CMV antigen and HVS, characteristically modulating CD8+ cell proliferation, thereby leading to reestablishment of the CD4/CD8 quotient. However, the proliferation induced by PHA was not inhibited. These results were produced on oral administration of acyclovir. Acyclovir modulates the lymphoproliferative response induced by CMV antigen. Based on this observation, the authors hypothesize that this immunomodulation may be related to its preventive effect on CMV disease in transplanted patients. 35. Sustained Release Floating Microspheres Of Acyclovir: Formulation, Optimization, Characterization And In Vitro Evaluation Directory of Open Access Journals (Sweden) Parmar Kunal Vinodbhai 2011-03-01 Full Text Available The aim of the present work was to prepare floating microspheres of acyclovir to prolong residence time in stomach and to sustain the release of acyclovir. Acyclovir loaded floating microspheres were prepared by double emulsion solvent evaporation method. The 32 full factorial design was applied to optimize the formulation. The resultant microspheres were evaluated for average particle size, percentage encapsulation efficiency, in vitro drug release and model fitting kinetics. Scanning electron microscopy, Fourier transform infrared (FTIR spectroscopy and differential scanning calorimetry were used to investigate the physical state of the drug in the microspheres. The particle size of microspheres was in the range of 275-340 µm. Percentage encapsulation efficiency was between 59%-77% w/w. Microspheres remained buoyant for more than about 12 h. The results of FT-IR spectroscopy and differential scanning calorimetry indicated the stable character of acyclovir in microspheres and also revealed absence of drugpolymer interaction. The in vitro drug release study showed that acyclovir release from the microspheres was slow and sustained for more than about 10 h. Drug release followed Korsemeyer-peppas model. The results of factorial batches revealed that the concentration of ethyl cellulose and stirring speed significantly affected drug encapsulation efficiency and particle size of the microspheres. Thus we can conclude that floating microspheres can successfully be developed to sustain the drug release. 36. Photolysis of three antiviral drugs acyclovir, zidovudine and lamivudine in surface freshwater and seawater. Science.gov (United States) Zhou, Chengzhi; Chen, Jingwen; Xie, Qing; Wei, Xiaoxuan; Zhang, Ya-nan; Fu, Zhiqiang 2015-11-01 Photodegradation is an important elimination process for many pharmaceuticals in surface waters. In this study, photodegradation of three antiviral drugs, acyclovir, zidovudine, and lamivudine, was investigated in pure water, freshwater, and seawater under the irradiation of simulated sunlight. Results showed that zidovudine was easily transformed via direct photolysis, while acyclovir and lamivudine were mainly transformed via indirect photolysis. We found that in freshwater, nitrate enhanced the photodegradation of the three antiviral drugs, bicarbonate promoted the photodegradation of acyclovir, and dissolved organic matter (DOM) accelerated the photolysis of acyclovir and lamivudine. In seawater, the photolysis of acyclovir was not susceptible to Cl(-), Br(-) and ionic strength; however, the photolysis of zidovudine was inhibited by Cl(-) and Br(-), and the photolysis of lamivudine was enhanced by Cl(-), Br(-) and ionic strength. Second-order reaction rate constants for the three antiviral drugs with (1)O2 (k1O2) and OH (kOH) were also measured. These results are important for fate and ecological risk assessment of the antiviral drugs in natural waters. 37. Mechanistic insights into acyclovir-polyethylene glycol 20000 binary dispersions Science.gov (United States) Venkateskumar, Krishnamoorthy; Parasuraman, Subramani; Gunasunderi, Raju; Sureshkumar, Krishnan; Nayak, M. Muralidhar; Shah, Syed Adnan Ali; Kassen, Khoo; Kai, Heng Wei 2016-01-01 Objective: The objective of this study is to provide a mechanistic insight into solubility enhancement and dissolution of acyclovir (ACY) by polyethylene glycol20000 (PEG20000). Materials and Methods: Solid dispersions with differing ratios of drug (ACY) and carrier (PEG20000) were prepared and evaluated by phase solubility, in vitro release studies, kinetic analysis, in situ perfusion, and in vitro permeation studies. Solid state characterization was also done by Powder X-Ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FT-IR) analysis and surface morphology was assessed by Polarizing Microscopic Image (PMI) analysis, Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Nuclear Magnetic Resonance (NMR) analysis. Results: Thermodynamic parameters proved the solubilization effect of carrier. The aqueous solubility and dissolution of ACY were increased in all samples. Formation of solid solution, crystallinity reduction, and absence of interaction between drug and carrier was proved by XRD, DSC, and FTIR analysis. The particle size reduction and change in surface morphology were confirmed by SEM and AFM and analysis. The permeation coefficient and amount of drug diffused was higher in samples as compared to ACY. The stability was high in dispersions, and it was proved by NMR analysis. Conclusion: The mechanical insights into the enhancement of solubility and dissolution could be used as a platform to improve the aqueous solubility for other poor water soluble drugs. PMID:28123988 38. [Diagnostic and therapeutic strategy for acyclovir-resistant herpes encephalitis]. Science.gov (United States) Saijo, Masayuki 2014-01-01 Acyclovir (ACV), which inhibits the replication of herpes simplex virus, is the standard drug for the treatment of herpes simplex encephalitis. Thanks to the introduction of ACV, the morbidity and mortality of HSE patients have significantly improved. However, the disease is still the severe infection, because it makes some patients with HSE suffer from severe consequences. The sensitivity test of the etiological HSV to ACV is very difficult due to the inability of isolation of the virus from cerebrospinal fluid (CSF). The cases of the ACV treatment-resistant HSE patients have been reported. However, these cases were not virologically confirmed. The first case of encephalitis in newborn baby with HSE caused by an

ACV-resistant HSV-1, which was virologically confirmed, was reported by our group. According to the sensitivity profile of the causative viruses to antiviral drugs, the drugs of choice for HSE should be properly considered. Strategy for diagnoses of HSE including antiviral sensitivity assessment and selection of drugs in HSE is reviewed. 39. Toxic effect of acyclovir on testicular tissue in rats. Science.gov (United States) Movahed, Elham; Nejati, Vahid; Sadrkhanlou, Rajabali; Ahmadi, Abbas 2013-02-01 Acyclovir (ACV), a synthetic purine nucleoside analogue, is known to be toxic to gonads. The current study evaluated cytotoxicity of ACV on histopathological changes in testis tissue and serum testosterone and lipid peroxidation concentrations of male rats. Animals were divided into five groups. One group served as control and one group served as control sham. In the drug treated groups ACV administered for 15 days. 18 days after the last injection, animals were sacrificed. Histopathological and histomorphometrical analysis of the testis was carried out. Serum levels of testosterone and Lipid Peroxidation and potential fertility of animals was evaluated. Male rats exposed to ACV had significant reduction in serum testosterone concentrations at 16 and 48mg/kg dose-levels (pACV induced histopathological changes in the testis and also increase the mean number of mast cells in peritubular or interstitial tissue in the testis at at 16 and 48mg/kg dose-levels (pACV caused increase of serum level of Lipid Peroxidation at 48mg/kg dose-level (pACV decreased potential fertility in male rats. The present results highly support the idea that ACV has adverse effect on the reproductive system in male rat. 40. Empiric acyclovir for neonatal herpes simplex virus infection. Science.gov (United States) Vanderpluym, Christina; Tawfik, Gerda; Hervas-Malo, Marilou; Lacaze-Masmonteil, Thierry; Kellner, James; Robinson, Joan L 2012-08-01 Because neonatal herpes simplex virus (NHSV) infection is difficult to diagnose, there has been a move towards using more empiric acyclovir (ACV). The purpose of this study was to review the use of ACV to optimize future management of NHSV. Charts were reviewed for infants started on intravenous ACV up to day 43 of life--January 2001 through February 2007--at five hospitals in Edmonton and Calgary. ACV was started for possible (N = 115) or proven (N = 3) herpes simplex virus (HSV) infection. Six of the infants with possible HSV infection later had proven HSV infection. Seizures (34%), hemodynamic instability (29%) and skin lesions (24%) were the most common indications for ACV. Among the 118 infants, 106 (90%) had cerebrospinal fluid obtained and 82 (69%) had at least one surface swab for HSV but 4 (3%) had no specimens submitted for HSV detection. ACV was continued for 3.9 ± 3.5 days in the infants with no proven HSV disease. Possible nephrotoxicity from ACV was recorded in 3 of these 109 infants and in none of the infants with proven HSV disease. Clinicians in Alberta primarily consider the diagnosis of NHSV infection when confronted with a neonate with seizures, hemodynamic instability or suspicious skin lesions, but need to consider the diagnosis more often if all cases are to be treated at first presentation. They often perform incomplete investigations to rule out NHSV infection. Adverse events from ACV appear to be uncommon when the drug is used for suspected NHSV disease. « 1 2 3 4 5 » « 1 2 3 4 5 » 41. In vitro Evaluation of Acyclovir/Chitosan Floating Systems. Science.gov (United States) Ruiz-Caro, Roberto; Veiga, MarÃa D 2010-12-06 Chitosan (CS) floating lyophilized formulations (L) for gastric drug delivery of acyclovir (ACV) have been developed. The freeze-dried formulations were obtained from acidic aqueous suspensions prepared with different ACV/CS ratios. No changes in ACV crystallinity were observed during X-ray diffraction powder studies as a consequence of the manufacturing process. Considering that fed and fasted states modified the intragastric pH, swelling and in vitro dissolution studies were carried out in different acidic media (0.1 M HCl and progressive pH medium) in order to understand the influence of these physiological states on ACV/CS formulations. Swelling behavior of the floating lyophilized formulations was dependent on CS and ACV proportions within L and on medium nature due to pH dependent CS solubility. Furthermore, no interactions between ACV and CS were detected in solid state according to the X-ray studies. In vitro dissolution of ACV from L was influenced by the swelling behavior. However, it is feasible to optimize the ACV/CS ratios to achieve a desired formulation that releases the total quantity of ACV at a specific time. Moreover, floatability was assessed by buoyancy tests. The results demonstrated that the freeze-drying process achieved effective floating systems capable of remaining within the stomach while the total amount of ACV is released from L. 42. Design and optimization of floating drug delivery system of acyclovir Directory of Open Access Journals (Sweden) Kharia A 2010-01-01 Full Text Available The purpose of the present work was to design and optimize floating drug delivery systems of acyclovir using psyllium husk and hydroxypropylmethylcellulose K4M as the polymers and sodium bicarbonate as a gas generating agent. The tablets were prepared by wet granulation method. A 32 full factorial design was used for optimization of drug release profile. The amount of psyllium husk (X1 and hydroxypropylmethylcellulose K4M (X2 were selected as independent variables. The times required for 50% (t 50% and 70% (t 70% drug dissolution were selected as dependent variables. All the designed nine batches of formulations were evaluated for hardness, friability, weight variation, drug content uniformity, swelling index, in vitro buoyancy, and in vitro drug release profile. All formulations had floating lag time below 3 min and constantly floated on dissolution medium for more than 24 h. Validity of the developed polynomial equation was verified by designing two check point formulations (C1 and C2. The closeness of predicted and observed values for t 50% and t 70% indicates validity of derived equations for the dependent variables. These studies indicated that the proper balance between psyllium husk and hydroxypropylmethylcellulose K4M can produce a drug dissolution profile similar to the predicted dissolution profile. The optimized formulations followed Higuchi′s kinetics while the drug release mechanism was found to be anomalous type, controlled by diffusion through the swollen matrix. 43. [A young patient of acute encephalitis complicated with acyclovir encephalopathy without renal dysfunction]. Science.gov (United States) Tomori, Koji; Isozumi, Kazuo; Motohashi, Sachiko; Komatsumoto, Satoru; Fukuuchi, Yasuo 2003-08-01 A previously healthy 30-year-old woman was admitted to our hospital because of impaired consciousness after convulsion. A temporary diagnosis of herpes simplex encephalitis was made, and intravenous acyclovir (ACV) therapy (250 mg four times daily in normal saline over 2 hours) was started. Three days later, she became confused, and was having hallucinations, dysarthria and generalized painful seizures occurred without focal neurologic deficit. Whether the neuropsychiatric symptoms were related to herpes simplex encephalitis or acyclovir neurotoxity was initially unclear. The brain MRI and lumbar puncture findings were initially normal, but abnormal FLAIR lesions appeared later. ACVassociated encephalopathy was considered. ACV was discontinued, and she recovered from the neurological disorder within 24 hours. Although blood levels of acyclovir were not determined, it is unlikely that they were in a toxic range, in view of her normal renal function. 44. Tissue necrosis following extravasation of acyclovir in an adolescent: A case report. Science.gov (United States) Neocleous, Charalambos; Andonopoulou, Eleni; Adramerina, Alkistis; Pegkou, Antigoni; Savelieva, Olga; Georgiadou, Petroula; Drikos, Ioannis 2017-05-01 Extravasation of intravenously infused vesicant solutions is a common problem in medical practice, which can lead to severe and progressive tissue dysfunction, ranging from persistent tissue oedema and fibrosis to delayed tissue necrosis. Acyclovir is a known vesicant medication administrated in paediatric patients, which appears to irritate venous and soft tissue if extravasated. We present the first case involving the extravasation of intravenously infused acyclovir in a female adolescent patient, which caused tissue necrosis and left behind a residual scar lesion. Nursing and medical staff should be aware of the potential dermatological side effects of intravenously infused acyclovir and other medications, even a long time after infusion, and the possible lack of initial local symptoms and signs. Early recognition of extravasation and prompt management are critical in preventing further morbidity, and optimizing outcomes. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina. 45. Acyclovir prodrug for the intestinal di/tri-peptide transporter PEPT1 DEFF Research Database (Denmark) Thomsen, Anne Engelbrecht; Christensen, Michael Søberg; Bagger, Morten Aavad 2004-01-01 as a measure for intracellular accumulation. In addition, bi-directional transport studies of Glu(acyclovir)-Sar across Caco-2 cell monolayers and in vitro metabolism studies of Glu(acyclovir)-Sar in various media of rat origin were performed. For these purposes HPLC-UV analysis was applied. Oral...... extracts. Bi-directional flux across Caco-2 cell monolayers apical to basolateral (FluxA-->B) and basolateral to apical (FluxB-->A) was measured and the FluxB-->A/FluxA-->B ratios of approximately 0.8 indicate that apical efflux mechanisms may not explain this lack of intracellular accumulation. These data... 46. Simultaneous delivery of tenofovir and acyclovir via an intravaginal ring. Science.gov (United States) Moss, John A; Malone, Amanda M; Smith, Thomas J; Kennedy, Sean; Kopin, Etana; Nguyen, Cali; Gilman, Josh; Butkyavichene, Irina; Vincent, Kathleen L; Motamedi, Massoud; Friend, David R; Clark, Meredith R; Baum, Marc M 2012-02-01 Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection "pod IVR" platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ± 335 μg day(-1) (ACV) and 321 ± 207 μg day(-1) (TFV); sheep, 174 ± 14 μg day(-1) (ACV) and 185 ± 34 μg day(-1) (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ± 7.31 μg ml(-1) (ACV) and 20.6 ± 16.2 μg ml(-1) (TFV); cervicovaginal lavage fluid, 118 ± 113 ng ml(-1) (ACV) and 191 ± 125 ng ml(-1) (TFV); tissue, 173 ng g(-1) (ACV) and 93 ng g(-1) (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens. 47. Enhanced dermal delivery of acyclovir using solid lipid nanoparticles. Science.gov (United States) Jain, Sanyog; Mistry, Meghal A; Swarnakar, Nitin K 2011-10-01 The present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir (ACV) and evaluate their potential as the carrier for dermal delivery. ACV-loaded SLNs (ACV-SLNs) were prepared by the optimized double emulsion process using Compritol 888 ATO as solid lipid. The prepared SLNs were smooth and spherical in shape with average diameter, polydispersity index, and entrapment efficiency of 262 ± 13 nm, 0.280 ± 0.01, and 40.08 ±†‰4.39% at 10% (w/w) theoretical drug loading with respect to Compritol 888 ATO content. Differential scanning calorimetry and powder X-ray diffraction pattern revealed that ACV was present in the amorphous state inside the SLNs. In vitro skin permeation studies on human cadaver and Sprague-Dawley rat skin revealed 17.65 and 15.17 times higher accumulation of ACV-SLNs in the dermal tissues in comparison to commercially available ACV cream after 24 h. Mechanism of topical permeation and dermal distribution was studied qualitatively using confocal laser scanning microscopy. While free dye (calcein) failed to penetrate skin barrier, the same encapsulated in SLNs penetrated deeply into the dermal tissue suggesting that pilosebaceous route was followed by SLNs for skin penetration. Histological examination and transdermal epidermal water loss measurement suggested that no major morphological changes occurred on rat skin surface due to the application of SLNs. Overall, it was concluded that ACV-loaded SLNs might be beneficial in improving dermal delivery of antiviral agent(s) for the treatment of topical herpes simplex infection. 48. Necrotizing Keratitis Caused by Acyclovir-Resistant Herpes Simplex Virus Directory of Open Access Journals (Sweden) Koji Toriyama 2014-10-01 Full Text Available Background: We report a case of necrotizing keratitis caused by acyclovir (ACV-resistant herpes simplex virus (HSV with a clinical appearance similar to a previous fungal keratitis infection. Methods: Observational case report. Results: Penetrating keratoplasty was performed in the left eye with a history of herpetic keratitis that resolved with periodic treatment with ACV ointment and a topical steroid. The left eye was painful and red with an abscess and corneal erosion in the peripheral donor cornea. Examination of the scraped corneal epithelium by light microscopy and culturing identified Candida albicans; polymerase chain reaction (PCR was negative for human herpes viruses. After antifungal treatment, the ocular pain gradually decreased and the lesions slowly improved but recurred with a similar clinical appearance. A second light microscopy examination and cultures were negative for pathogens including C. albicans. PCR was positive for HSV-1 DNA; treatment with 3% topical ACV ointment was unsuccessful. A third examination showed only HSV-1 DNA. Despite antiviral ACV ointment, no clinical improvement occurred based on the HSV DNA copy numbers, which were the same before and after treatment, indicating a possible ACV-resistant strain. When topical trifluorothymidine was substituted for ACV, clinical improvement occurred and the HSV DNA copy numbers decreased. Conclusion: Necrotizing keratitis induced by ACV-resistant HSV occurred independently after fungal keratitis, with a similar clinical appearance in this case, making diagnosis and treatment difficult. Monitoring the HSV DNA load by real-time PCR could be useful for refractory cases even with atypical clinical appearances. 49. Acyclovir prophylaxis predisposes to antiviral-resistant recurrent herpetic keratitis. Science.gov (United States) van Velzen, Monique; van de Vijver, David A M C; van Loenen, Freek B; Osterhaus, Albert D M E; Remeijer, Lies; Verjans, Georges M G M 2013-11-01 Long-term acyclovir (ACV) prophylaxis, recommended to prevent recurrent herpes simplex virus type 1 (HSV-1) ocular disorders, may pose a risk for ACV-refractory disease due to ACV resistance. We determined the effect of ACV prophylaxis on the prevalence of corneal ACV-resistant (ACV(R)) HSV-1 and clinical consequences thereof in patients with recurrent HSV-1 keratitis (rHK). Frequencies of ACV(R) viruses were determined in 169 corneal HSV-1 isolates from 78 rHK patients with a history of stromal disease. The isolates' ACV susceptibility profiles were correlated with clinical parameters to identify risk factors predisposing to ACV(R) rHK. Corneal HSV-1 isolates with >28% ACV(R) viruses were defined as ACV(R) isolates. Forty-four isolates (26%) were ACV-resistant. Multivariate analyses identified long-term ACV prophylaxis (≥12 months) (odds ratio [OR] 3.42; 95% confidence interval [CI], 1.32-8.87) and recurrence duration of ≥45 days (OR 2.23; 95% CI, 1.02-4.87), indicative of ACV-refractory disease, as independent risk factors for ACV(R) isolates. Moreover, a corneal ACV(R) isolate was a risk factor for ACV-refractory disease (OR 2.28; 95% CI, 1.06-4.89). The data suggest that long-term ACV prophylaxis predisposes to ACV-refractory disease due to the emergence of corneal ACV(R) HSV-1. ACV-susceptibility testing is warranted during follow-up of rHK patients. 50. Acyclovir: a new use for an old drug. Science.gov (United States) Vanpouille, Christophe; Lisco, Andrea; Margolis, Leonid 2009-12-01 Epidemiological studies have demonstrated that HIV-1 and herpes simplex virus-2 (HSV-2) are responsible for two epidemics and that, by overlapping in risk populations, they reinforce the spreading of both HIV-1 disease and genital herpes. Randomized controlled trials have investigated whether acyclovir (ACV), a synthetic drug designed to suppress herpes viruses, might provide an inexpensive and safe way to drastically reduce HIV-1 spreading around the world. The controversial results of these trials are reviewed below in light of the recent discovery of the direct suppression of HIV-1 by ACV. Recent studies have shown that although ACV therapy does not prevent HIV-1 transmission, it decreases plasma, genital, rectal, and seminal HIV-1 RNA levels. The decrease of HIV-1 load has been believed to be the result of an indirect mechanism and explained by reduction of HSV2-mediated inflammation. The discovery of the direct inhibitory activity of ACV on HIV-1 reverse transcriptase brings new insights into the interpretation of these results. Also, it is important to understand why HSV-2-suppressive therapy with ACV did not reduce HIV-1 acquisition/transmission. The direct suppression of HIV-1 by ACV activated by coinfecting HSV-2 may in part explain the ACV-induced decrease of HIV load reported in several clinical trials. If this is the case, other herpes viruses capable of ACV activation may contribute to this effect. New basic studies and new targeted clinical trials are needed to understand whether ACV therapy can also be beneficial for HSV-2-negative patients. These studies will show whether ACV therapy should be included in HIV-1 treatment as well as whether ACV-based drugs specifically targeting HIV-1 can be developed. 51. Pharmacokinetics of Stereoisomeric Dipeptide Prodrugs of Acyclovir Following Intravenous and Oral Administrations in Rats: A Study Involving In vivo Corneal Uptake of Acyclovir Following Oral Dosing Directory of Open Access Journals (Sweden) Ravi S.Talluri 2009-10-01 Full Text Available Objective: To delineate the plasma pharmacokinetics and determine the corneal uptake of valine based stereoisomeric dipeptide prodrugs of acyclovir (ACV in rats. Methods: Male Sprague-Dawley rats were used for the study. Pharmacokinetics of ACV, L-valine-acyclovir (LACV, L-valine- D-valine-acyclovir (LDACV and D-valine-Lvaline acyclovir (DLACV prodrugs were delineated. These compounds were administered intravenously as a bolus via jugular vein cannula and orally by gavage. Samples were purified by protein precipitation method and analyzed by LC-MS/MS. Pertinent pharmacokinetic parameters were obtained by using WinNonlin. Corneal uptake studies of LDACV and LACV were studied following oral administration. Results: Following i.v. administration, the area under the curve (AUC in µM*min of generated ACV was in the order of LACV › LDACV › DLACV indicating their rate of metabolism. The AUC values of total drug obtained in the systemic circulation after oral administration LACV and LDACV were 1077.93 ± 236.09 and 1141.76 ± 73.67 µM*min, respectively. DLACV exhibited poor oral absorption. Cmax (µM and AUC of the intact prodrug obtained in the systemic circulation following oral administration of LDACV were almost 4–5 times higher than LACV. Moreover, concentrations achieved in the cornea after oral administration of LDACV were almost two times of LACV. Conclusions: LDACV increased both the oral bioavailability and subsequent in vivo corneal uptake of ACV. Hence, LDACV can be considered as the most promising drug candidate for delivery of ACV, in treatment of both genital herpes and ocular herpes keratitis after oral administration. 52. Long-term ultra-low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation. Science.gov (United States) Asano-Mori, Yuki; Kanda, Yoshinobu; Oshima, Kumi; Kako, Shinichi; Shinohara, Akihito; Nakasone, Hideki; Sato, Hiroyuki; Watanabe, Takuro; Hosoya, Noriko; Izutsu, Koji; Asai, Takashi; Hangaishi, Akira; Motokura, Toru; Chiba, Shigeru; Kurokawa, Mineo 2008-06-01 To evaluate the efficacy of long-term prophylaxis with ultra-low-dose acyclovir against varicella-zoster virus (VZV) reactivation, we analyzed the records of 242 Japanese adult patients who underwent allogeneic hematopoietic stem cell transplantation for the first time from 1995 to 2006 at our hospital. We started long-term oral acyclovir at 200 mg/day in July 2001. Acyclovir was continued until the end of immunosuppressive therapy and at least 1 year after transplantation. Sixty-six patients developed VZV reactivation at a median of 248 days after HSCT, with a cumulative incidence of 34.7%. Only one breakthrough reactivation occurred during long-term acyclovir, which responded well to therapeutic dose of valacyclovir. The use of long-term acyclovir was the only independent determinant that significantly decreased the overall incidence of VZV reactivation (20% vs. 50%, P < 0.0001). With this prophylaxis, visceral dissemination and serious complications other than post-herpetic neuralgia was completely eliminated, and thereby need for hospitalization was significantly reduced (21% vs. 71%, P = 0.0034). Fifteen of the 57 patients who discontinued acyclovir developed VZV reactivation, with a cumulative incidence of 32.1%. VZV reactivation following discontinuation tended to occur in patients who were receiving immunosuppressive therapy at the cessation of acyclovir. These findings suggested that long-term prophylaxis of ultra-low-dose acyclovir resulted in a successful prevention of severe VZV-related symptoms and death, with a significantly decreased overall incidence of VZV reactivation. Prolongation of prophylactic acyclovir on profound immunosuppression might be important for thorough suppression of VZV reactivation. 53. Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis NARCIS (Netherlands) R. Duan (Rui); R.D. de Vries (Rory); A.D.M.E. Osterhaus (Ab); L. Remeijer (Lies); G.M.G.M. Verjans (George) 2008-01-01 textabstractThe prevalence and molecular characteristics of isolates from 173 immunocompetent patients with herpetic keratitis (HK) whowere infected with acyclovir (ACV)resistant(ACVR) corneal herpes simplex virus (HSV)-1 was determined. Isolates from 11 (6.4%) of the patients were ACVR, and 9 of t 54. Prevalence of intrathecal acyclovir resistant virus in herpes simplex encephalitis patients NARCIS (Netherlands) J.G. Mitterreiter (Johanna G.); M.J. Titulaer (Maarten); G.P. van Nierop (Gijsbert); J.J.A. van Kampen (Jeroen); G.I. Aron; A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George); W.J.D. Ouwendijk (Werner ) 2016-01-01 textabstractHerpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted 55. Influence of Low Cetyltrimethylammonium Bromide Concentration on the Interactions and Properties of Hemoglobin with Acyclovir Institute of Scientific and Technical Information of China (English) LIU Tian-Qing; GUO Rong 2006-01-01 The effects of cetyltrimethylammonium bromide (CTAB) on the properties of hemoglobin (Hb) at low CTAB concentration were studied in Hb/acyclovir/CTAB system by the methods of UV-Vis spectrum, fluorescence, zeta potential, conductivity and negative-staining transmission electron microscope (TEM). With the increase of CTAB concentration, the UV peak intensity at 276 nm, the intrinsic fluorescence, the zeta potential of Hb and the system conductivity were all enhanced. Hb was easily oxidized to oxyHb and hemichrome. In Hb/acyclovir/CTAB system,CTAB made the UV-Vis spectrum, fluorescence, conductivity and conformation of Hb tend to be returned to those of the original Hb but the zeta potential not to do so. The UV absorption peak of Hb-acyclovir complex disappeared,and the tight structure of Hb aroused by acyclovir was refolded. When CTAB concentration was higher than 5 ×10-5 mol/L, the two absorption peaks at 536 and 576 nm appeared again, and the Hb structure became looser again. 56. Effect of oral acyclovir after penetrating keratoplasty for herpetic keratitis: a placebo-controlled multicenter trial. NARCIS (Netherlands) Rooij, J.G.M. van; Rijneveld, W.J.; Remeijer, L.; Volker-Dieben, H.J.; Eggink, C.A.; Geerards, A.J.; Mulder, P.G.H.; Doornenbal, P.; Beekhuis, W.H. 2003-01-01 OBJECTIVE: To determine the prophylactic effect of oral acyclovir on the recurrence rate of herpetic eye disease after penetrating keratoplasty. DESIGN: A randomized, doublemasked, placebo-controlled multicenter trial. PARTICIPANTS: Sixty-eight consecutive patients (68 eyes) with corneal opacities 57. A Randomized Double-Blind Placebo Controlled Trial of Oral Acyclovir in Renal Allograft Recipients Directory of Open Access Journals (Sweden) Walter F Schlech 1993-01-01 Full Text Available Fifty renal transplant patients were randomized to receive either 800 mg acyclovir by mouth four times daily or identical placebo tablets for prophylaxis of herpes

simplex infection. Patients were followed weekly to assess reactivation of herpes simplex, varicella zoster virus, Epstein-Barr virus or cytomegalovirus (CMV infections. The patients received standard immunosuppressive regimens including cyclosporine A. Acyclovir suppressed secretion of herpes simplex virus in treated patients (P=0.001. Three episodes of mucocutaneous herpes simplex virus occurred in placebo recipients and one in a noncompliant acyclovir recipient. A clinically important difference in graft survival was demonstrated, but because of sample size failed to reach statistical significance (P=0.11. No reactivation of varicella zoster virus, Epstein-Barr virus or CMV infection was detected in either group. Toxicity was limited to central nervous irritability. The authors conclude that high dose oral acyclovir provides effective prophylaxis for prevention of herpes simplex virus infections in renal transplantation and may be associated with increased graft survival, perhaps from suppression of CMV infection. 58. Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis NARCIS (Netherlands) R. Duan (Rui); R.D. de Vries (Rory); A.D.M.E. Osterhaus (Albert); L. Remeijer (Lies); G.M.G.M. Verjans (George) 2008-01-01 textabstractThe prevalence and molecular characteristics of isolates from 173 immunocompetent patients with herpetic keratitis (HK) whowere infected with acyclovir (ACV)resistant(ACVR) corneal herpes simplex virus (HSV)-1 was determined. Isolates from 11 (6.4%) of the patients were ACVR, and 9 of 59. Prevalence of intrathecal acyclovir resistant virus in herpes simplex encephalitis patients NARCIS (Netherlands) J.G. Mitterreiter (Johanna G.); M.J. Titulaer (Maarten); G.P. van Nierop (Gijsbert); J.J.A. van Kampen (Jeroen); G.I. Aron; A.D.M.E. Osterhaus (Albert); G.M.G.M. Verjans (George); W.J.D. Ouwendijk (Werner ) 2016-01-01 textabstractHerpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted 60. [Open clinical trial with oral acyclovir for the prophylaxis of disease by Cytomegalovirus in low risk liver transplant recipients]. Science.gov (United States) Moreno, J; Montero, J L; Gavilán, F; Costán, G; Herrero, C; Cárdenas, M; Sánchez-Guijo, P; Torre-Cisneros, J 1999-10-01 Checking the first 70 low risk liver transplantation performed in our hospital, who did not receive prophylaxis for Cytomegalovirus, we found that the incidence of Cytomegalovirusinfection and Cytomegalovirus-disease were 47% and 16% respectively. For this reason we started a prospective, open clinical study, to address the safety of acyclovir prophylaxis in low-risk liver transplant patients. Seventy patients did not receive acyclovir. Fifty patients received oral acyclovir during 3 months (800-3,200 mg/day). The occurrence of Cytomegalovirus infection was not modified (40%) but Cytomegalovirus disease decreased dramatically (4%, p Varicela-zoster symptomatic disease in this group of patients. « 1 2 3 4 5 » « 2 3 4 5 6 » 61. Enzyme-catalyzed Transesterification of Unusual Substrate: Synthesis of Acyclovir and L-ascorbic Acid (Vitamin C) Vinyl Esters Institute of Scientific and Technical Information of China (English) æ— 2003-01-01 The synthesis of acyclovir and L-ascorbic acid with divinyladipate was performed with alkaline protease from Bacillus subtilis and lipase from Lipozyme (immobilized from Mucor miehei) in different anhydrous organic solvents. Two corresponding derivatives were obtained. 62. Determination of Acyclovir in Human Plasma Samples by HPLC Method with UV Detection: Application to Single-Dose Pharmacokinetic Study Directory of Open Access Journals (Sweden) Dragica Zendelovska 2015-03-01 CONCLUSION: Good precision, accuracy, simplicity, sensitivity and shorter time of analysis of the method makes it particularly useful for processing of multiple samples in a limited period of time for pharmacokinetic study of acyclovir. 63. [Combined treatment supported by piracetam and/or acyclovir in idiopathic sudden sensorineural hearing loss: experience with 81 cases]. Science.gov (United States) Karakurt, Süleyman Emre; Ozkul, Mehmet DoÄŸan; Cukurova, Ibrahim; Demirhan, Erhan; YiÄŸitbaÅŸi, Orhan Gazi 2009-01-01 To investigate the efficiency of piracetam and acyclovir in treating sudden hearing loss. Eightyone patients (44 males, 37 females; mean age 40.4 year; range 18 to 72 years) who had treatment between January 2002 and December 2006 with diagnosis of idiopathic sudden hearing loss were evaluated retrospectively. These patients were divided into four groups according to the treatment they received. The patients who had combined treatment constituted the first group; those who had combined treatment and piracetam the second; those who had combined treatment and acyclovir the third; those who had combined treatment, acyclovir, and piracetam the fourth group. For the four treatment groups, in the pre-and post-treatment (10th day) evaluation of the treatment efficiency made by calculation of the hearing thresholds in 250-8000 Hz frequencies, no significant difference between the groups was determined (p>0.05). No additional benefit was obtained with acyclovir and piracetam in treatment. 64. Valacyclovir versus acyclovir for the treatment of herpes zoster ophthalmicus in immunocompetent patients. Science.gov (United States) Schuster, Alexander K; Harder, Björn C; Schlichtenbrede, Frank C; Jarczok, Marc N; Tesarz, Jonas 2016-11-14 Herpes zoster ophthalmicus affects the eye and vision, and is caused by the reactivation of the varicella zoster virus in the distribution of the first division of the trigeminal nerve. An aggressive management of acute herpes zoster ophthalmicus with systemic antiviral medication is generally recommended as the standard first-line treatment for herpes zoster ophthalmicus infections. Both acyclovir and its prodrug valacyclovir are medications that are approved for the systemic treatment of herpes zoster. Although it is known that valacyclovir has an improved bioavailability and steadier plasma concentration, it is currently unclear as to whether this leads to better treatment results and less ocular complications. To assess the effects of valacyclovir versus acyclovir for the systemic antiviral treatment of herpes zoster ophthalmicus in immunocompetent patients. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register; 2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), Web of Science Conference Proceedings Citation Index-Science (CPCI-S; January 1990 to June 2016), BIOSIS Previews (January 1969 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016. We considered all randomised controlled trials (RCTs) in which systemic valacyclovir was compared to systemic acyclovir medication for treatment of herpes zoster ophthalmicus. There were no language restrictions. Two review authors independently selected trials, evaluated the risk of bias in included trials, and extracted and analysed 65. A Randomized, Double-blind, Placebo-Controlled Study of Efficacy of Oral Acyclovir in the Treatment of Pityriasis Rosea. Science.gov (United States) Ganguly, Satyaki 2014-05-01 Pityriasis rosea is an acute self-limiting skin disorder of unknown aetiology. Recently human herpes virus 6 and 7 has been hypothesized to be the cause of pityriasis rosea. To determine the efficacy of acyclovir, an anti-viral drug, in the treatment of pityriasis rosea. A randomized, double-blind, placebo-controlled study of efficacy of oral acyclovir in the treatment of pityriasis rosea was conducted on 73 patients. Thirty eight randomly selected patients were started on oral acyclovir. Thirty-five patients were prescribed placebo. The patients as well as the chief investigator were unaware of the therapeutic group to which patients belonged (acyclovir or placebo). Patients in both the groups were evaluated clinically after 7 and 14 days following the first visit and the data were analysed. Follow up data of 60 patients was available and these were included in the statistical analysis. 53.33% and 86.66% of the patients belonging to the acyclovir group showed complete resolution on the 7(th) day and 14(th) day respectively following the first visit compared to 10% and 33.33% of patients from the placebo group. The findings were statistically significant. The study showed that high dose acyclovir is effective in the treatment of pityriasis rosea. 66. Multicenter randomized study of inosine pranobex versus acyclovir in the treatment of recurrent herpes labialis and recurrent herpes genitalis in Chinese patients. Science.gov (United States) You, Yi; Wang, Li; Li, Yafei; Wang, Qianqiu; Cao, Shuanglin; Tu, Yating; Li, Shenqiu; Bai, Li; Lu, Jianyun; Wei, Zhiping; Chen, Wenchieh; Hao, Fei 2015-06-01 The objective of the study is to evaluate the efficacy and safety of oral inosine pranobex as compared with acyclovir in the treatment of recurrent herpes labialis (RHL) and recurrent herpes genitalis (RHG). A multicenter double-blind, double-dummy, randomized, controlled, parallel group trial was conducted in 144 patients with RHL and 144 RHG. Patients were assigned to treatment in one of two groups: (i) inosine pranobex group (active inosine pranobex, 1 g four times daily, and acyclovir placebo); or (ii) acyclovir group (active acyclovir, 200 mg five times daily, and inosine pranobex placebo). The total symptom score (TSS) of patients with RHL did not differ in the inosine pranobex and acyclovir group on the 3rd or 7th day of treatment. There was also no difference in the efficacy rates between the two groups. No difference of TSS was observed between patients with RHG taking inosine pranobex and acyclovir on days 3 or 5 of the treatment, respectively. The short-term clinical recurrence rate of RHG at 3-month follow-up was much lower in the inosine pranobex group than acyclovir group. The incidence of hyperuricemia was higher in the inosine pranobex group than acyclovir group. In conclusion, inosine pranobex was as effective as acyclovir in treating RHL and RHG with significantly greater reduction of the short-term recurrence rate of herpes genitalis at 3-month follow up. Long-term recurrence rates at 6 months or longer remain to be determined. Hyperuricemia should be monitored during the treatment. 67. Differential scanning calorimetry as a screening technique in compatibility studies of acyclovir extended release formulations Energy Technology Data Exchange (ETDEWEB) Barboza, Fernanda M.; Vecchia, Debora D. [Universidade Estadual de Ponta Grossa (UEPG), PR (Brazil). Dept. de Ciencias Farmaceuticas. Lab. de Controle de Qualidade; Tagliari, Monika P.; Ferreira, Andrea Granada; Silva, Marcos A.S.; Stulzer, Hellen K., E-mail: [email protected] [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Dept. de Ciencias Farmaceuticas. Lab. de Controle de Qualidade 2009-07-01 Acyclovir (ACV) has been investigated during the past years, mainly due to its antiviral activity. Assessment of possible incompatibility between an active component and different excipients along with the evaluation of thermal stability are crucial parts of a normal study prior to the final formulation setting of a medicine. Thermal analysis studies were used as important and complementary tools during pre-formulation to determine the compatibility of drug excipients with the purpose of developing an acyclovir extended release formulation. Fourier transform infrared spectroscopy and X-ray powder diffraction analyses were also realized. The results showed that ACV only exhibited interaction which could influence the stability of the product in the binary mixtures of ACV/magnesium stearate. (author) 68. Acyclovir and hydrocortisone cream for the early treatment of recurrent cold sores Directory of Open Access Journals (Sweden) Carrie A Sailer 2011-01-01 Full Text Available Carrie A Sailer1, Spotswood L Spruance2, Christopher M Hull11Department of Dermatology, 2Department of Medicine, Division of Infectious Diseases, University of Utah, Salt Lake City, USAAbstract: Current antiviral therapies for herpes simplex labialis primarily reduce healing time. Since the host immune response also plays a role in both controlling recurrent infection as well as producing clinical symptoms, new studies are showing efficacy using topical corticosteroids. This review will evaluate the safety and efficacy of 5% acyclovir–1% hydrocortisone cream (Xereseâ„¢[US], Xerclear®[Europe] for treatment of patients with herpes simplex labialis. A large, randomized, doubleblind, placebo-controlled study recently demonstrated that treatment with 5% acyclovir–1% hydrocortisone cream significantly decreased the percentage of ulcerative lesions, reduced lesion healing time, and decreased mean lesion area compared with both topical acyclovir alone and vehicle.Keywords: herpes labialis, herpes simplex virus, HSV, acyclovir, hydrocortisone, ME-609, Xerese, Xerclear 69. [Preauricular injection of betamethasone depot and acyclovir for the treatment of acute herpes zoster ophthalmicus]. Science.gov (United States) Arenas-Archila, E; Alvizu, F; Muñoz-Sarmiento, D 2015-04-01 Several treatments have been described for the management of patients with herpes zoster ophthalmicus (HZO). However, the progress of these patients is usually slow, and many of them develop postherpetic neuritis (PHN). In the present paper, three clinical cases are presented, in which a significant symptomatic improvement was obtained by using a preauricular injection of a mixture of betamethasone depot combined with acyclovir. PHN did not develop in any of them. The preauricular injection of betamethasone depot and acyclovir could be a good alternative for the management of HZO. Copyright © 2013 Sociedad Española de OftalmologÃa. Published by Elsevier España, S.L.U. All rights reserved. 70. Structural and Theoretical Evidence of the Depleted Proton Affinity of the N3-Atom in Acyclovir Directory of Open Access Journals (Sweden) Esther VÃlchez-RodrÃguez 2016-10-01 Full Text Available The hydronium salt (H3O2[Cu(N7–acv2(H2O2(SO42]·2H2O (1, acv = acyclovir has been synthesized and characterized by single-crystal X-ray diffraction and spectral methods. Solvated Cu(OH2 is a by-product of the synthesis. In the all-trans centrosymmetric complex anion, (a the Cu(II atom exhibits an elongated octahedral coordination; (b the metal-binding pattern of acyclovir (acv consists of a Cu–N7(acv bond plus an (aquaO–H···O6(acv interligand interaction; and (c trans-apical/distal sites are occupied by monodentate O-sulfate donor anions. Neutral acyclovir and aqua-proximal ligands occupy the basal positions, stabilizing the metal binding pattern of acv. Each hydronium(1+ ion builds three H-bonds with O–sulfate, O6(acv, and O–alcohol(acv from three neighboring complex anions. No O atoms of solvent water molecules are involved as acceptors. Theoretical calculations of molecular electrostatic potential surfaces and atomic charges also support that the O-alcohol of the N9(acv side chain is a better Hacceptor than the N3 or the O-ether atoms of acv. 71. Comparing the effect of diode laser against acyclovir cream for the treatment of herpes labialis. Science.gov (United States) Honarmand, Marieh; Farhadmollashahi, Leila; Vosoughirahbar, Ehsan 2017-06-01 Recently alternative therapies such as the use of diode laser therapy have been introduced for recurrent herpes labial infection. The aim of this study was to evaluate the effectiveness of diode laser for treatment of recurrent herpes labialis. This was single-blind randomized clinical trial to evaluate the efficacy of diode laser for the treatment of recurrent herpes labial. In total, 60 patients whit recurrent herpes simplex labialis were selected and randomly divided in to three groups. 20 patients received treatment whit diode laser (at a wavelength of 870 nm, energy density 4.5 j/cm2), 20 patients were treated with acyclovir cream 5%, 20 patients received treatment with laser-off (placebo). The end point was lesions crusting. Data analyzed by Tukey HSD Test and One-way ANOVA (at a significance level of 0.05) in SPSS-20 software. The mean length of recovery time (day) in the laser, off laser, and acyclovir groups was 2.20±0.41, 4.30±1.03, and 3.4±1.142, respectively. There is a significant difference between three groups in this regard (Pcream. Key words:Recurrent herpes labial, Acyclovir, Low level laser therapy. 72. Oxidation of the antiviral drug acyclovir and its biodegradation product carboxy-acyclovir with ozone: kinetics and identification of oxidation products. Science.gov (United States) Prasse, Carsten; Wagner, Manfred; Schulz, Ralf; Ternes, Thomas A 2012-02-21 The oxidation of the antiviral drug acyclovir (ACV) and its main biotransformation product carboxy-acyclovir (carboxy-ACV) by ozone was investigated. Both compounds have recently been detected in surface water, and carboxy-ACV has also been detected in drinking water. The experiments revealed a strong pH dependence of the oxidation of ACV and carboxy-ACV with reaction rate constants increasing by 4 orders of magnitude between the protonated, positively charged form (k(ox,PH(+)), ∼2.5 × 10(2) M(-1) s(-1)) and the deprotonated, negatively charged form (k(ox,P(-)), 3.4 × 10(6) M(-1) s(-1)). At pH 8 a single oxidation product was formed which was identified via LC-LTQ-Orbitrap MS and NMR as N-(4-carbamoyl-2-imino-5-oxoimidazolidin)formamido-N-methoxyacetic acid (COFA). Using Vibrio fischeri , an acute bacterial toxicity was found for COFA while carboxy-ACV revealed no toxic effects. Ozonation experiments with guanine and guanosine at pH 8 led to the formation of the respective 2-imino-5-oxoimidazolidines, confirming that guanine derivatives such as carboxy-ACV are undergoing the same reactions during ozonation. Furthermore, COFA was detected in finished drinking water of a German waterworks after ozonation and subsequent activated carbon treatment. 73. Antiviral and virucidal activity of Chelidonium majus L. extract compared with Acyclovir against Herpes simplex virus type 1 Directory of Open Access Journals (Sweden) M Sadeghpour Natanzi 2017-02-01 Full Text Available Background and aim: Herpes simplex virus is one of the most important human pathogenic viruses that may lead to oral herpes, keratoconjunctivitis and even encephalitis. A number of enzymes of the virus such as DNA polymerase can be targeted antiviral drugs. Acyclovir is used to treat infections of the virus, today due to drug resistance, need to do more research on finding new drugs, especially herbal medicines has increased. This study aimed to investigate the antiviral effect of methanol extract of Chelidonium majus compared with acyclovir against the virus in HeLa cell culture. Methods: In this experimental study, the toxicity of Chelidonium majus L. methanol extract and acyclovir on HeLa cell was determined with both MTT and Trypan blue methods. The antiviral effect of Chelidonium majus L. extract and acyclovir was evaluated in different concentration (1800- 1700- 1600- 1500- 1400 and 500- 100- 75- 50- 30-10 µg/ml and also in different times before, after and during of virus adsorption respectively. The virus titer was measured by tissue culture infectious dose 50 TCID50(  method. The T-test method was used to comparing the effects of both compounds on virus. Results: The maximum non-toxic concentration of Chelidonium majus L. extract on HeLa cell was determined 1600 µg/ml that has the maximum inhibitory effect on HSV-1 replication. Acyclovir was shown low toxicity on HeLa cells.The 30 µg/ml concentration of acyclovir was considered for the next steps of the study.The highest inhibitory effect of the extract was observed 1 hour after absorption and the virus replication was suppressed completely by the acyclovir immediately after virus adsorption up to 8 hours after infection. Conclusion: The Chelidonium majus L. methanol extract has less effect than the acyclovir on inhibition of herpes simplex virus replication in a first few hours of infection. More research is needed to achieve effective compounds with antiviral activity of above 74. The comparison between the efficacy of high dose acyclovir and erythromycin on the period and signs of pitiriasis rosea Directory of Open Access Journals (Sweden) Ehsani Amirhooshang 2010-01-01 Full Text Available Background: Pityriasis Rosea (PR is an acute inflammatory and self-limiting skin disorder, sometimes with troublesome symptoms. To date, there are few treatments available for this disorder. Aim: Compare the traditional treatment with erythromycin to a newly introduced antiviral treatment acyclovir for PR. Materials and Methods: Patients with clinically confirmed diagnosis of PR, matching our exclusion criteria, were enrolled. They were randomized in two groups that received high-dose oral acyclovir or erythromycin. The participants were evaluated two, four, and eight weeks after commencement of the study and followed for one year. Results: A total of 30 patients including 15 males and 15 females completed the study. After eight weeks, 13 patients in the acyclovir group experienced complete response, while in the erythromycin group only six patients had complete response (P < 0.05. Also, patients in the acyclovir group experienced faster resolution of pruritus in comparison with the erythromycin group (not significant. No adverse drug reaction was detected in both groups. Conclusion: It seemed that a high-dose of oral acyclovir was a safe and effective therapy for PR, although this remained to be confirmed in larger studies. 75. Evaluation of the effects of acyclovir and/or human amniotic membrane on herpes virus culture and quantitative virus inactivity by real-time polymerase chain reaction Directory of Open Access Journals (Sweden) Feride Aylin Kantarci 2014-08-01 Full Text Available AIM: To investigate the permeability of amniotic membrane in herpes virus cell culture to acyclovir with real time polymerase chain reaction (RTPCR.METHODS: Madin-Darby Bovine Kidney (MDBK cell culture and Bovine Herpes Virus (BHV1 type 1 were used in the study. Cell cultures were grouped into two on the basis of herpes virus inoculation. Each group was sub-grouped into three. Amniotic membrane (V-HAM, acyclovir (V-A, and amniotic membrane and acyclovir (V-HAM-A were applied to these subgroup cultures, respectively. After the application of the membrane and the drug, the cultures were evaluated at 24 and 48h for cytopathic effect positive (CPE+ with a tissue culture microscope. In the CPE (+ samples, the DNA was extracted for viral DNA analysis by RT-PCR.RESULTS: In control cultures without herpes virus CPE was not detected. Besides, amniotic membrane and acyclovir did not have cytotoxic effect on cell cultures. CPE were detected in Bovine Herpesvirus type-1 inoculated cell cultures after amniotic membrane and/or acyclovir application. DNA analysis with RT-PCR indicated that Cycle threshold (Ct values were lower in the BHV1 and membrane applied group (amniotic membrane group< acyclovir group< membrane and acyclovir group. This showed that membrane did not have antiviral effect. The membrane and acyclovir cell culture groups with high Ct values indicated that membrane was permeable and had a low barrier effect to drug,CONCLUSION: In our in-vitro study, we found that amniotic membrane, which can be used in the treatment of corneal diseases, did not have antiviral effect. Besides, we detected that amniotic membrane was permeable to acyclovir in BHV-1 inoculated MDBK cell culture. However, more studies are necessary to investigate the quantitative effects of amniotic membrane and acyclovir. 76. Evaluation of the effects of acyclovir and/or human amniotic membrane on herpes virus culture and quantitative virus inactivity by real-time polymerase chain reaction Institute of Scientific and Technical Information of China (English) Feride; Aylin; Kantarci; Ali; Reza; Faraji; Aykut; Ozkul; Fikret; Akata 2014-01-01 ·AIM: To investigate the permeability of amniotic membrane in herpes virus cell culture to acyclovir with real time polymerase chain reaction(RT-PCR).·METHODS: MadinDarby Bovine Kidney(MDBK) cell culture and Bovine Herpes Virus(BHV1) type 1 were used in the study. Cell cultures were grouped into two on the basis of herpes virus inoculation. Each group was sub-grouped into three. Amniotic membrane(V-HAM),acyclovir(V-A), and amniotic membrane and acyclovir(V-HAM-A) were applied to these subgroup cultures,respectively. After the application of the membrane and the drug, the cultures were evaluated at 24 and 48 h for cytopathic effect positive(CPE +) with a tissue culture microscope. In the CPE(+) samples, the DNA was extracted for viral DNA analysis by RT-PCR.·RESULTS: In control cultures without herpes virus CPE was not detected. Besides, amniotic membrane and acyclovir did not have cytotoxic effect on cell cultures.CPE were detected in Bovine Herpesvirus type-1inoculated cell cultures after amniotic membrane and/or acyclovir application. DNA analysis with RT-PCR indicated that Cycle threshold(Ct) values were lower in the BHV1 and membrane applied group(amniotic membrane group < acyclovir group < membrane and acyclovir group). This showed that membrane did not have antiviral effect. The membrane and acyclovir cell culture groups with high Ct values indicated thatmembrane was permeable and had a low barrier effect to drug.·CONCLUSION: In our in-vitro study, we found that amniotic membrane, which can be used in the treatment of corneal diseases, did not have antiviral effect. Besides,we detected that amniotic membrane was permeable to acyclovir in BHV-1 inoculated MDBK cell culture.However, more studies are necessary to investigate the quantitative effects of amniotic membrane and acyclovir.

77. Amino acid substitutions in the thymidine kinase gene of induced acyclovir-resistant herpes simplex virus type 1 Science.gov (United States) Hussin, Ainulkhir; Nor, Norefrina Shafinaz Md; Ibrahim, Nazlina 2013-11-01 Acyclovir (ACV) is an antiviral drug of choice in healthcare setting to treat infections caused by herpes viruses, including, but not limited to genital herpes, cold sores, shingles and chicken pox. Acyclovir resistance has emerged significantly due to extensive use and misuse of this antiviral in human, especially in immunocompromised patients. However, it remains unclear about the amino acid substitutions in thymidine (TK) gene, which specifically confer the resistance-associated mutation in herpes simplex virus. Hence, acyclovirresistant HSV-1 was selected at high concentration (2.0 - 4.5 μg/mL), and the TK-gene was subjected to sequencing and genotypic characterization. Genotypic sequences comparison was done using HSV-1 17 (GenBank Accesion no. X14112) for resistance-associated mutation determination whereas HSV-1 KOS, HSV-1 473/08 and HSV clinical isolates sequences were used for polymorphism-associated mutation. The result showed that amino acid substitutions at the non-conserved region (UKM-1: Gln34Lys, UKM-2: Arg32Ser & UKM-5: Arg32Cys) and ATP-binding site (UKM-3: Tyr53End & UKM-4: Ile54Leu) of the TK-gene. These discoveries play an important role to extend another dimension to the evolution of acyclovir-resistant HSV-1 and suggest that selection at high ACV concentration induced ACV-resistant HSV-1 evolution. These findings also expand the knowledge on the type of mutations among acyclovir-resistant HSV-1. In conclusion, HSV-1 showed multiple strategies to exhibit acyclovir resistance, including amino acid substitutions in the TK gene. 78. Evaluation of cross-linked chitosan microparticles containing acyclovir obtained by spray-drying Energy Technology Data Exchange (ETDEWEB) Stulzer, Hellen Karine [Laboratorio Quitech, Departamento de Quimica, Universidade Federal de Santa Catarina (Brazil); Laboratorio de Controle de Qualidade, Departamento de Ciencias Farmaceuticas, Universidade Federal de Santa Catarina (Brazil); Laboratorio de Controle de Qualidade, Departamento de Ciencias Farmaceuticas, Universidade Estadual de Ponta Grossa (Brazil)], E-mail: [email protected]; Tagliari, Monika Piazzon [Laboratorio de Controle de Qualidade, Departamento de Ciencias Farmaceuticas, Universidade Federal de Santa Catarina (Brazil); Parize, Alexandre Luis [Laboratorio Quitech, Departamento de Quimica, Universidade Federal de Santa Catarina (Brazil); Silva, Marcos Antonio Segatto [Laboratorio de Controle de Qualidade, Departamento de Ciencias Farmaceuticas, Universidade Federal de Santa Catarina (Brazil); Laranjeira, Mauro Cesar Marghetti [Laboratorio Quitech, Departamento de Quimica, Universidade Federal de Santa Catarina (Brazil) 2009-03-01 The aim of this study was to obtain microparticles containing acyclovir (ACV) and chitosan cross-linked with tripolyphosphate using the spray-drying technique. The resultant system was evaluated through loading efficiency, differential scanning calorimetry (DSC), thermogravimetric analysis (TG), X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), in vitro release and stability studies. The results obtained indicated that the polymer/ACV ratio influenced the final properties of the microparticles, with higher ratios giving the best encapsulation efficiency, dissolution profiles and stability. The DSC and XRPD analyses indicated that the ACV was transformed into amorphous form during the spray-drying process. 79. Acyclovir-loaded sorbitan esters-based organogel: development and rheological characterization. Science.gov (United States) Rajpoot, Kuldeep 2017-05-01 Herein, a nanoemulsion-based organogel (NEOG) system loaded with acyclovir has been developed for the effective treatment of herpes simplex virus infection via topical delivery. Pseudo-ternary phase diagram exhibited increase in non-birefrigent, optically isotropic region of organogel with Smix (Kw) ratio. The NEOG C showed good storage (G') and loss moduli (G″), and more compact network structures. Gel-sol transition temperature (Tg) and fractal dimension (Df) of NEOG system revealed increased density of the tubular network with Kw. Hence, high gelling ability of the developed NEOG system may attribute to the combination of sustained and site-specific delivery of drugs. 80. Formulation and evaluation of acyclovir nanosuspension for enhancement of oral bioavailability Directory of Open Access Journals (Sweden) Mangesh Ramesh Bhalekar 2014-01-01 Full Text Available Acyclovir, an antiviral drug used against herpes simplex virus and varicella zoster virus. The dose ranges between 200 and 800 mg and the oral bioavailability is 10-20%, which decreases as the dose is increased. The aim of this research work was to formulate and characterize nanosuspensions of acyclovir with an intention to increase the oral bioavailability. Nanosuspensions were prepared by the precipitation-ultra sonication method and the effects of important process parameters i.e., precipitation temperature, stirring speed, end point temperature of probe sonicator, energy input and sonication time were investigated systematically, the optimal nanosuspension (particle size 274 nm was obtained at values of 4°C, 10,000 rpm, 30°C, 600 Watt and 20 min, respectively. The nanosuspension was lyophilized using different matrix formers and sucrose (100% w/w to drug was found to prevent agglomeration and particle size upon reconstitution was found to be 353 nm. The lyophilized nanocrystals appeared flaky in scanning electron microscopy images, the X-ray powder diffraction and differential scanning calorimetry analysis showed the nanoparticles to be in the crystalline state. Ex vivo permeation study for calculating absorption rate and in vivo bioavailability area under the curve both showed three-fold increase over marketed suspension. « 2 3 4 5 6 » « 3 4 5 6 7 » 81. Cellulose Acetate 398-10 Asymmetric Membrane Capsules for Osmotically Regulated Delivery of Acyclovir Directory of Open Access Journals (Sweden) Alka Sonkar 2016-01-01 Full Text Available The study was aimed at developing cellulose acetate asymmetric membrane capsules (AMCs of acyclovir for its controlled delivery at the absorption site. The AMCs were prepared by phase inversion technique using wet process. A 23 full factorial design assessed the effect of independent variables (level(s of polymer, pore former, and osmogen on the cumulative drug release from AMCs. The buoyant optimized formulation F7 (low level of cellulose acetate; high levels of both glycerol and sodium lauryl sulphate displayed maximum drug release of 97.88±0.77% in 8 h that was independent of variation in agitational intensity and intentional defect on the cellulose acetate AMC. The in vitro data best fitted zero-order kinetics (r2=0.9898. SEM micrograph of the transverse section confirmed the asymmetric nature of the cellulose acetate capsular membrane. Statistical analysis by Design Expert software indicated no interaction between the independent variables confirming the efficiency of the design in estimating the effects of variables on drug release. The optimized formulation F7 (desirability = 0.871 displayed sustenance of drug release over the drug packed in AMC in pure state proving the superiority of osmotically active formulation. Conclusively the AMCs have potential for controlled release of acyclovir at its absorption site. 82. Polymorphs of acyclovir-maleic acid salt and their reversible phase transition Science.gov (United States) Wang, Lianyan; Zhao, Yumei; Zhang, Zhengfeng; Wang, Jianming; Wang, Qiang; Zheng, Zhibing; Deng, Zongwu; Zhang, Hailu 2017-01-01 Acyclovir is a commonly used antiviral drug while its solubility is far from satisfied. It was reported that 1:1 acyclovir-maleic acid salt (ACV-MAL) possesses much higher maximum apparent solubility. In this contribution, a new crystal structure of ACV-MAL was solved at room temperature. This new crystal structure and previously reported structure at low temperature can transform to each other via a reversible solid phase transformation, which has been confirmed by single-crystal X-ray diffraction, solid state NMR and cycling differential scanning calorimetry tests. The phase change temperature is ca. 283-293 K (10-20 °C), which is slightly lower than room temperature (298 ± 2 K/25 ± 2 °C), but is in the range of ambient temperature. This kind of near room temperature phase transformation is less concerned and tends to be neglected. This case report reminds that more attention should be paid to the polymorphism of pharmaceuticals at such temperature range due to its fundamental and practical significance. 83. Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels for controlled drug delivery of acyclovir Science.gov (United States) Malik, Nadia Shamshad; Ahmad, Mahmood; Minhas, Muhammad Usman 2017-01-01 To explore the potential role of polymers in the development of drug-delivery systems, this study investigated the use of β-cyclodextrin (β-CD), carboxymethyl cellulose (CMC), acrylic acid (AA) and N’ N’-methylenebis-acrylamide (MBA) in the synthesis of hydrogels for controlled drug delivery of acyclovir (ACV). Different proportions of β-CD, CMC, AA and MBA were blended with each other to fabricate hydrogels via free radical polymerization technique. Fourier transform infrared spectroscopy (FTIR) revealed successful grafting of components into the polymeric network. Thermal and morphological characterization confirmed the formation of thermodynamically stable hydrogels having porous structure. The pH-responsive behaviour of hydrogels has been documented by swelling dynamics and drug release behaviour in simulated gastrointestinal fluids. Drug release kinetics revealed controlled release behaviour of the antiviral drug acyclovir in developed polymeric network. Cross-linked β-cyclodextrin and carboxymethyl cellulose hydrogels can be used as promising candidates for the design and development of controlled drug-delivery systems. PMID:28245257 84. Synergistic penetration of ethosomes and lipophilic prodrug on the transdermal delivery of acyclovir. Science.gov (United States) Zhou, Yan; Wei, Yu-Hui; Zhang, Guo-Qiang; Wu, Xin-An 2010-04-01 The aim of this study was to investigate the lipophilic prodrug as a means of promoting acyclovir (ACV) that exhibited biphasic insolubility into the ethosomes for optimum skin delivery. Acyclovir Palmitate (ACV-C(16)) was synthesized as the lipophilic prodrug of ACV. The ethosomal system and the liposomal system bearing ACV or ACV-C(16) were prepared, respectively. The systems were characterized for shape, zeta potential value, particle size, and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy were used for the percutaneous absorption studies. The results showed that the entrapment efficiency of ACV-C(16) ethosomes (87.75%) were much higher than that of ACV ethosomes (39.13%). The quantity of drug in the skin from ACV-C(16) ethosomes at the end of the 24 h transdermal experiment (622.89 microg/cm(2)) was 5.30 and 3.43 times higher than that from ACV-C(16) hydroalcoholic solution and ACV ethosomes, respectively. This study indicated that the binary combination of the lipophilic prodrug ACVC(16) and the ethosomes synergistically enhanced ACV absorption into the skin. 85. Development and Validation of Acyclovir HPLC External Standard Method in Human Plasma: Application to Pharmacokinetic Studies Directory of Open Access Journals (Sweden) Selvadurai Muralidharan 2014-01-01 Full Text Available A simple, rapid, and selective RP-HPLC method was developed for the estimation of acyclovir in human plasma. The method involves a simple protein precipitation technique. Chromatographic separation was carried out on a reverse phase C18 column using mixture of 5 mM ammonium acetate (pH 4.0 and acetonitrile (40†‰: 60, v/v at a flow rate of 1.0 mL/min with UV detection at 290 nm. The retention time of acyclovir was 4.12 minutes. The method was validated and found to be linear in the range of 25.0–150.0 ng/mL. Validation studies were achieved by using the fundamental parameters, including accuracy, precision, selectivity, sensitivity, linearity and range, stability studies, limit of detection (LOD, and limit of quantitation (LOQ. It shows recovery at 91.0% which is more precise and accurate compared to the other method. These results indicated that the bioanalytical method was linear, precise, and accurate. The new bioanalytical method was successfully applied to a pharmacokinetic linearity study in human plasma. 86. Pemphigus vulgaris in a patient with arthritis and uveitis: successful treatment with immunosuppressive therapy and acyclovir. Science.gov (United States) Pranteda, G; Carlesimo, M; Bottoni, U; Di Napoli, A; Muscianese, M; Pimpinelli, F; Cordiali, P; Laganà , B; Pranteda, G; Di Carlo, A 2014-01-01 A case of pemphigus vulgaris in a 41-year-old man with undifferentiated arthritis and uveitis is described. Histology of labial mucosa showed acantholytic, necrotic, and multinucleated giant keratinocytes having some nuclear inclusions suggestive of a virus infection. Specific serological tests revealed IgG positivity for HSV-1, CMV, and EBV, while real-time polymerase chain reaction assay from a biopsy of the mucosal lesion showed the presence of HSV-1/2 DNA. Treatment with prednisone, methotrexate, and acyclovir induced the complete remission of mucosal and joint symptoms, which then relapsed after interruption of antiviral therapy or immunosuppressive therapy. Therefore, a combined treatment with low doses of prednisone, methotrexate, and acyclovir was restarted and during 18 months of follow-up no recurrence was registered. Correlations between pemphigus and the herpes virus infection and also between autoimmune arthritis and herpetic agents have been well documented, but the exact role of the herpes virus in these disorders still needs further discussion. Our case strongly suggests that when autoimmune disorders do not respond to immunosuppressive agents, a viral infection should be suspected, researched, and treated. 87. Formulation and evaluation of mucoadhesive buccal patch of acyclovir utilizing inclusion phenomenon Directory of Open Access Journals (Sweden) Ankita Saxena 2011-12-01 Full Text Available Mucoadhesive buccal patch releasing drug in the oral cavity at a predetermined rate may present distinct advantages over traditional dosage forms, such as tablets, gels and solutions. A buccal patch for systemic administration of acyclovir in the oral cavity was developed using polymers hydroxy propyl methyl cellulose (K4M, hydroxy propyl methyl cellulose (K15M, sodium carboxy methyl cellulose and poly vinyl pyrolidone (K30, plasticizer poly ethylene glycol (400 and a backing membrane of Eudragit (RL100. The films were evaluated in terms of swelling, residence time, mucoadhesion, release, and organoleptic properties. The optimized films showed lower release as compared to controlled drug delivery systems. Hence, an inclusion complex of acyclovir was prepared with hydrophilic polymer hydroxylpropyl beta-cyclodextrin in the molar ratio of 1:1. The inclusion complex was characterized by optical microscopy, FAB mass spectroscopy, and FTIR spectroscopy. Patches formulated with the acyclovir inclusion complex were evaluated along the same lines as those containing acyclovir alone. The in vitro release data revealed a substantial increase from 64.35% to 88.15% in the case of PS I and PS II batches, respectively, confirming the successful use of inclusion complexes for the formulation of buccal patch of acyclovir.Mucoadesivos bucais liberadores de fármacos para a cavidade oral com taxa de liberação pré-determinada podem apresentar distintas vantagens em relação à s formas farmacêuticas convencionais como comprimidos, géis e soluções. Neste trabalho, um adesivo bucal para administração sistêmica de aciclovir através da cavidade oral foi desenvolvido empregando-se os polÃmeros hidroxipropilmetil celulose (K4M, hidroxipropilmetil celulose (K15M, carboximetil celulose sódica e polivinil pirrolidona (K30, polietilenoglicol plastificado (400 e uma membrana suporte de Eudragit (RL100. Os filmes obtidos foram avaliados em termos de 88. Disposition kinetics of a dipeptide ester prodrug of acyclovir and its metabolites following intravenous and oral administrations in rat. Science.gov (United States) Talluri, Ravi S; Gaudana, Ripal; Hariharan, Sudharshan; Jain, Ritesh; Mitra, Ashim K 2009-01-01 The objective of this work was to study the disposition kinetics of valine-valine-acyclovir (VVACV), a dipeptide ester prodrug of acyclovir following intravenous and oral administrations in rat. A validated LC-MS/MS analytical method was developed for the analysis VVACV, Valine-Acyclovir (VACV), and Acyclovir (ACV) using a linear Ion Trap Quadrupole. ACV was administered orally for comparison purpose. In the VVACV group, both blood and urine samples and in the ACV group only blood samples were collected. All the samples were analyzed using LC-MS/MS. The LLOQ for ACV, VACV, and VVACV were 10, 10, and 50 ng/ml, respectively. Relevant pharmacokinetic parameters were obtained by non-compartmental analyses of data with WinNonlin. Following i.v. administration of VVACV, AUC(0-inf) (min*µM) values for VVACV, VACV, and ACV were 55.06, 106, and 466.96, respectively. The AUC obtained after oral administration of ACV was 178.8. However, following oral administration of VVACV, AUC(0-inf) values for VACV and ACV were 89.28 and 810.77, respectively. Thus the exposure of ACV obtained following oral administration of VVACV was almost 6-fold higher than ACV. This preclinical pharmacokinetic data revealed that VVACV has certainly improved the oral bioavailability of ACV and is an effective prodrug for oral delivery of ACV. 89. The Influence of Chitosan on the Oral Bioavailability of Acyclovir-a Comparative Bioavailability Study in Humans NARCIS (Netherlands) Kubbinga, M.; Nguyen, M.A.; Staubach, P.; Teerenstra, S.; Langguth, P. 2015-01-01 PURPOSE: The effects of chitosan hydrochloride on the oral absorption of acyclovir in humans were studied to confirm the absorption enhancing effects reported for in vitro and rat studies, respectively. METHODS: A controlled, open-label, randomized, 3-phase study was conducted in 12 healthy human vo 90. Influences of Triton X-100 on Hemoglobin Behaviors in Hemoglobin/Acyclovir/Triton X-100/H2O System Institute of Scientific and Technical Information of China (English) LIU,Tian-Qing; GUO,Rong 2007-01-01 The influences of Triton X-100 on hemoglobin(Hb)behaviors were studied by the methods of UV-Vis spectrum,fluorescence spectrum,HPLC,conductivity,zeta potential and negative-staining transmission electron microscope in Hb/acyclovir/Triton X-100/H2O system.With the increase of Triton X-100 concentration in the system,the percentage of the free acyclovir increased from 58%-63% to 90%-94%.The static quenching constant and the association number of acyclovir to Hb decreased.The fluorescence spectrum,conductivity,zeta potential,fluorescence polarization and negative-staining morphology of Hb tended to recover to those of the original state of Hb in the same concentration of Hb.The interaction between Triton X-100 and Hb is stronger than that between acyclovir and Hb.Most Triton-X-100 was associated with Hb at low Triton X-100 concentration.But the interaction of Triton X-100 with Hb was apparently dominant in high Triton X-100 concentration.The Hb structure was unfolded and finally denatured. 91. The Influence of Chitosan on the Oral Bioavailability of Acyclovir-a Comparative Bioavailability Study in Humans NARCIS (Netherlands) Kubbinga, M.; Nguyen, M.A.; Staubach, P.; Teerenstra, S.; Langguth, P. 2015-01-01 PURPOSE: The effects of chitosan hydrochloride on the oral absorption of acyclovir in humans were studied to confirm the absorption enhancing effects reported for in vitro and rat studies, respectively. METHODS: A controlled, open-label, randomized, 3-phase study was conducted in 12 healthy human 92. Latent acyclovir-resistant herpes simplex virus type 1 in trigeminal ganglia of immunocompetent individuals. Science.gov (United States) van Velzen, Monique; van Loenen, Freek B; Meesters, Roland J W; de Graaf, Miranda; Remeijer, Lies; Luider, Theo M; Osterhaus, Albert D M E; Verjans, Georges M G M 2012-05-15 Specific mutations within the hypervariable herpes simplex virus (HSV) gene thymidine kinase (TK) gene lead to acyclovir (ACV) resistance. To uncover the existence of latent ACV-resistant (ACV(R)) HSV-1, we determined the genetic and functional variability of the HSV-1 TK gene pool in paired trigeminal ganglia (TG) of 5 immunocompetent individuals. The latent virus pool consisted of a donor-specific HSV-1 quasispecies, including one major ACV-sensitive (ACV(S)) and multiple phylogenetic-related minor ACV(S) and ACV(R) TK variants. Contrary to minor variants, major TK variants were shared between paired TG. The data demonstrate the coexistence of phylogenetic-related ACV(S) and ACV(R) latent HSV-1 in human TG. 93. Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis. Science.gov (United States) Duan, Rui; de Vries, Rory D; Osterhaus, Albert D M E; Remeijer, Lies; Verjans, Georges M G M 2008-09-01 The prevalence and molecular characteristics of isolates from 173 immunocompetent patients with herpetic keratitis (HK) who were infected with acyclovir (ACV)-resistant (ACV(R)) corneal herpes simplex virus (HSV)-1 was determined. Isolates from 11 (6.4%) of the patients were ACV(R), and 9 of these 11 patients were refractory to therapy with ACV; the ACV(R) isolates from 5 and 1 of these 9 patients were cross-resistant to gancyclovir and to both gancyclovir and foscarnet, respectively. Of the 11 ACV(R) isolates, 10 had, in the thymidine kinase gene, mutations that presumably conferred the ACV(R) phenotype. These data demonstrate a relatively high prevalence of corneal HSV-1 ACV(R) isolates in patients with HK, which emphasizes the need to monitor for ACV susceptibility in patients with HK who are refractory to therapy with ACV. 94. Comparative permeability of some acyclovir derivatives through native mucus and crude mucin dispersions. Science.gov (United States) Legen; Kristl, A 2001-08-01 The permeability of some guanine derivatives (acyclovir [ACV], deoxyacyclovir [DCV], and their N-acetyl congeners) through native porcine mucus and crude porcine mucin dispersions (30% and 50% w/v) was investigated in two-compartment dialysis cells. High correlation between apparent permeability coefficients Papp of tested substances determined in these two models was observed, although the examined compounds permeated faster through the native mucus. It was also established that Papp values decrease with increasing hydrophilicity and molecular mass of the tested substances. Furthermore, the influence of some substances that affect mucus structure (cysteine, N-acetylcysteine [NCY], sodium taurocholate [ST], and sodium chloride) on the permeation rate of the examined compounds through mucus and mucin dispersions was examined. It was shown that the Papp values of guanine derivatives were generally lower after the addition of these substances to the native mucus and mucin dispersions, although the lowering effect was more pronounced in the case of native mucus. 95. SEARCH OF INHIBITORS OF HERPES VIRAL REPLICATION: 30 YEARS AFTER ACYCLOVIR Directory of Open Access Journals (Sweden) Korovina A. N. 2013-08-01 Full Text Available Analysis of study and using of different chemical compounds as inhibitors of herpes virus replication is given in the review. However, it does not apply for full details of all the studies on active antiherpetic drugs finding. It’s been over 30 years since the discovery of the first antiherpetic drugs ? acyclovir. Meanwhile, lots of active chemical compounds appeared that have been brought to the antiviral drugs. An essential understanding of strategies for finding drugs came in, one of which was establishment of depot forms of antiherpetic drugs. On the basis of the vast published experimental material the authors concluded that the study of the herpes virus and search for inhibitors of its replication is still an important issue and requires the efforts of chemists, biologists, pharmacists. 96. The effects of dexamethasone and acyclovir on a cell culture model of delayed facial palsy. Science.gov (United States) Turner, Meghan T; Nayak, Shruti; Kuhn, Maggie; Roehm, Pamela Carol 2014-04-01 Pretreatment with antiherpetic medications and steroids decreases likelihood of development of delayed facial paralysis (DFP) after otologic surgery. Heat-induced reactivation of herpes simplex virus type 1 (HSV1) in geniculate ganglion neurons (GGNs) is thought to cause of DFP after otologic surgery. Antiherpetic medications and dexamethasone are used

to treat DFP. Pretreatment with these medications has been proposed to prevent development of DFP. Rat GGN cultures were latently infected with HSV1 expressing a lytic proteinGFP chimera. Cultures were divided into pretreatment groups receiving acyclovir (ACV), acyclovir-plus-dexamethasone (ACV + DEX), dexamethasone alone (DEX), or untreated media (control). After pretreatment, all cultures were heated 43°C for 2 hours. Cultures were monitored daily for reactivation with fluorescent microscopy. Viral titers were determined from culture media. Heating cultures to 43°C for 2 hours leads to HSV1 reactivation and production of infectious virus particles (59 ± 6.8%); heating cultures to 41 °C showed a more variable frequency of reactivation (60 ± 40%), compared with baseline rates of 14.4 ± 5%. Cultures pretreated with ACV showed lower reactivation rates (ACV = 3.7%, ACV + DEX = 1.04%) compared with 44% for DEX alone. Viral titers were lowest for cultures treated with ACV or ACV + DEX. GGN cultures harboring latent HSV1 infection reactivate when exposed to increased temperatures that can occur during otologic surgery. Pretreatment with ACV before heat provides prophylaxis against heatinduced HSV reactivation, whereas DEX alone is associated with higher viral reactivation rates. This study provides evidence supporting the use of prophylactic antivirals for otologic surgeries associated with high rates of DFP. 97. Acyclovir Injection Science.gov (United States) ... effects of your treatment using laboratory tests and physical examinations. It is important to keep all appointments ... health care provider as soon as possible: tenderness warmth irritation drainage redness swelling pain 98. Acyclovir Lauriad(®): a muco-adhesive buccal tablet for the treatment of recurrent herpes labialis. Science.gov (United States) Downing, Christopher; Moayyad, Jonathan; Tamirisa, Aparna; Tyring, Stephen 2014-03-01 The treatment of recurrent herpes labialis remains a challenge in the 21st century. The virus is ubiquitous and there is no vaccine against the disease. Although recurrence episodes are usually of shorter duration than the primary episode, they are debilitating to patients and there is significant stigma associated with the disease. Acyclovir Lauriad(®) is a new topical agent that was approved by the US FDA in 2013 for the treatment of recurrent herpes labialis, which affects approximately 20-40% of the population worldwide. The drug is a muco-adhesive tablet, applied to the upper gum at the onset of prodromal symptoms. Utilizing Lauriad(®) technology, a biologically active compound traverses the mucous membrane to deliver a high concentration of acyclovir directly to the site of the herpes simplex virus infection. Data from a Phase III clinical trial shows that this may be a promising therapy for patients with recurrent herpes labialis. 99. Acyclovir Prophylaxis Reduces the Incidence of Herpes Zoster Among HIV-Infected Individuals: Results of a Randomized Clinical Trial. Science.gov (United States) Barnabas, Ruanne V; Baeten, Jared M; Lingappa, Jairam R; Thomas, Katherine K; Hughes, James P; Mugo, Nelly R; Delany-Moretlwe, Sinead; Gray, Glenda; Rees, Helen; Mujugira, Andrew; Ronald, Allan; Stevens, Wendy; Kapiga, Saidi; Wald, Anna; Celum, Connie 2016-02-15 Human immunodeficiency virus (HIV)-infected persons have higher rates of herpes zoster than HIV-uninfected individuals. We assessed whether twice daily treatment with 400 mg of oral acyclovir reduces the incidence of herpes zoster in a randomized, double-blind, placebo-controlled trial among 3408 persons coinfected with HIV and herpes simplex virus type 2. During 5175 person-years of follow-up, 26 cases of herpes zoster occurred among those assigned acyclovir, compared with 69 cases among those assigned placebo (rates, 1.00 and 2.68/100 person-years, respectively), a relative decrease of 62% (hazard ratio, 0.38; 95% confidence interval, .24-.67; P herpes zoster incidence among HIV-infected persons. 100. Comparison of the Efficacy of Combination Therapy of Prednisolone-Acyclovir with Prednisolone Alone in Bell’s Palsy Directory of Open Access Journals (Sweden) Ali KHAJEH 2015-06-01 Full Text Available How to Cite This Article: Khajeh A, Fayyazi A, Soleimani Gh, Miri-Aliabad Gh, Shaykh Veisi S, Khajeh B. Comparison of the Efficacy ofCombination Therapy of Prednisolone-Acyclovir with Prednisolone Alone in Bell’s Palsy. Iran J Child Neurol. Spring 2015; 9(2:17-20.AbstractObjectiveBell’s palsy is a rapid onset, usually, unilateral paralysis of the facial nerve that causes significant changes in an individual’s life such as a decline in personal, social, and educational performance. This study compared efficacy of combined prednisolone and acyclovir therapy with prednisolone alone.Materials & MethodsThis study is a randomized controlled trial conducted on 43 Children (2–18 years old with Bell’s palsy. The first group of 23 patients was treated with prednisolone and the remaining patients were treated with a combination of prednisolone and acyclovir. The required data were extracted, using an informational form based on the House-Brackmann Scale, which grades facial nerve paralysis. The data were analyzed with Mann-Whitney test using SPSS version 16.ResultsThe mean age of the first and second group were 8.65 ± 5.07 and 8.35 ± 4.92 years, respectively, (p=0.84. Sixty one percent and 39% of patients in the first group, and 45% and 55% of patients in the second group were male and female, respectively. No significant differences exist between the groups in terms of age and gender. The rate of complete recovery was 65.2% in group I and 90% in the group II (p=0.04.ConclusionThe results of this study showed that the combined prednisolone and acyclovir therapy of patients with Bell’s palsy is far more effective than treatment with prednisolone alone. Actually, age and gender had no impact on the rate of recovery. « 3 4 5 6 7 » « 4 5 6 7 8 » 101. Chitosan and Kappa-Carrageenan Vaginal Acyclovir Formulations for Prevention of Genital Herpes. In Vitro and Ex Vivo Evaluation Science.gov (United States) Sánchez-Sánchez, MarÃa-Pilar; MartÃn-Illana, Araceli; Ruiz-Caro, Roberto; Bermejo, Paulina; Abad, MarÃa-José; Carro, Rubén; Bedoya, Luis-Miguel; Tamayo, Aitana; Rubio, Juan; Fernández-Ferreiro, Anxo; Otero-Espinar, Francisco; Veiga, MarÃa-Dolores 2015-01-01 Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations have been developed for the controlled release of acyclovir, which may prevent the sexual transmission of the herpes simplex virus. Drug release studies were carried out in two media: simulated vaginal fluid and simulated vaginal fluid/simulated seminal fluid mixture. The bioadhesive capacity and permanence time of the bioadhesion, the prepared compacts, and compacted granules were determined ex vivo using bovine vaginal mucosa as substrate. Swelling processes were quantified to confirm the release data. Biocompatibility was evaluated through in vitro cellular toxicity assays, and the results showed that acyclovir and the rest of the materials had no cytotoxicity at the maximum concentration tested. The mixture of hydroxyl-propyl-methyl-cellulose with chitosan- or kappa-carrageenan-originated mucoadhesive systems that presented a complete and sustained release of acyclovir for a period of 8–9 days in both media. Swelling data revealed the formation of optimal mixed chitosan/hydroxyl-propyl-methyl-cellulose gels which could be appropriated for the prevention of sexual transmission of HSV. PMID:26393621 102. Chitosan and Kappa-Carrageenan Vaginal Acyclovir Formulations for Prevention of Genital Herpes. In Vitro and Ex Vivo Evaluation Directory of Open Access Journals (Sweden) MarÃa-Pilar Sánchez-Sánchez 2015-09-01 Full Text Available Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations have been developed for the controlled release of acyclovir, which may prevent the sexual transmission of the herpes simplex virus. Drug release studies were carried out in two media: simulated vaginal fluid and simulated vaginal fluid/simulated seminal fluid mixture. The bioadhesive capacity and permanence time of the bioadhesion, the prepared compacts, and compacted granules were determined ex vivo using bovine vaginal mucosa as substrate. Swelling processes were quantified to confirm the release data. Biocompatibility was evaluated through in vitro cellular toxicity assays, and the results showed that acyclovir and the rest of the materials had no cytotoxicity at the maximum concentration tested. The mixture of hydroxyl-propyl-methyl-cellulose with chitosan- or kappa-carrageenan-originated mucoadhesive systems that presented a complete and sustained release of acyclovir for a period of 8–9 days in both media. Swelling data revealed the formation of optimal mixed chitosan/hydroxyl-propyl-methyl-cellulose gels which could be appropriated for the prevention of sexual transmission of HSV. 103. Turning an antiviral into an anticancer drug: nanoparticle delivery of acyclovir monophosphate. Science.gov (United States) Yao, Jing; Zhang, Yuan; Ramishetti, Srinivas; Wang, Yuhua; Huang, Leaf 2013-09-28 Anti-herpes simplex virus (HSV) drug acyclovir (ACV) is phosphorylated by the viral thymidine kinase (TK), but not the cellular TK. Phosphorylated ACV inhibits cellular DNA synthesis and kills the infected cells. We hypothesize that ACV monophosphate (ACVP), which is an activated metabolite of ACV, should be efficient in killing cells independent of HSV-TK. If so, ACVP should be a cytotoxic agent if properly delivered to the cancer cells. The Lipid/Calcium/Phosphate (LCP) nanoparticles (NPs) with a membrane/core structure were used to encapsulate ACVP to facilitate the targeted delivery of ACVP to the tumor. The LCP NPs showed entrapment efficiency of ~70%, the nano-scaled particle size and positive zeta potential. Moreover, ACVP-loaded LCP NPs (A-LCP NPs) exhibited concentration-dependent cytotoxicity against H460 cells and increased S-phase arrest. More importantly, a significant reduction of the tumor volume over 4 days following administration (pACV and ACVP) and blank LCP NPs showed little or no therapeutic effect. It was also found that the high efficacy of A-LCP NPs was associated with the ability to induce dramatic apoptosis of the tumor cells, as well as significantly inhibit tumor cell proliferation and cell cycle progression. In conclusion, with the help of LCP NPs, monophosphorylation modification of ACV can successfully modify an HSV-TK-dependent antiviral drug into an anti-tumor drug. 104. Inclusion complex of the antiviral drug acyclovir with cyclodextrin in aqueous solution and in solid phase Directory of Open Access Journals (Sweden) Carlos von Plessing Rossel 2000-12-01 Full Text Available Complexation between acyclovir (ACV, an antiviral drug used for the treatment of herpes simplex virus infection, and beta-cyclodextrin (beta-CD was studied in solution and in solid states. Complexation in solution was evaluated using solubility studies and nuclear magnetic resonance spectroscopy (¹H-NMR. In the solid state, X-ray diffraction, differential scanning calorimetry (DSC, thermal gravimetric analysis (TGA and dissolution studies were used. Solubility studies suggested the existence of a 1:1 complex between ACV and beta-CD. ¹H-NMR spectroscopy studies showed that the complex formed occurs with a stoichiometry ratio of 1:1. Powder X-ray diffraction indicated that ACV exists in a semicrystalline state in the complexed form with beta-CD. DSC studies showed the existence of a complex of ACV with beta-CD. The TGA studies confirmed the DSC results of the complex. Solubility of ACV in solid complexes was studied by the dissolution method and it was found to be much more soluble than the uncomplexed drug. 105. Preparation and characterization of nanoparticles of carboxymethyl cellulose acetate butyrate containing acyclovir Science.gov (United States) Vedula, Venkata Bharadwaz; Chopra, Maulick; Joseph, Emil; Mazumder, Sonal 2016-02-01 Nanoparticles of carboxymethyl cellulose acetate butyrate complexed with the poorly soluble antiviral drug acyclovir (ACV) were produced by precipitation process and the formulation process and properties of nanoparticles were investigated. Two different particle synthesis methods were explored—a conventional precipitation method and a rapid precipitation in a multi-inlet vortex mixer. The particles were processed by rotavap followed by freeze-drying. Particle diameters as measured by dynamic light scattering were dependent on the synthesis method used. The conventional precipitation method did not show desired particle size distribution, whereas particles prepared by the mixer showed welldefined particle size ~125-450 nm before and after freeze-drying, respectively, with narrow polydispersity indices. Fourier transform infrared spectroscopy showed chemical stability and intactness of entrapped drug in the nanoparticles. Differential scanning calorimetry showed that the drug was in amorphous state in the polymer matrix. ACV drug loading was around 10 wt%. The release studies showed increase in solution concentration of drug from the nanoparticles compared to the as-received crystalline drug. 106. Proteomic characterization of acyclovir-induced nephrotoxicity in a mouse model. Science.gov (United States) Lu, Hong; Han, Ya-Juan; Xu, Jia-Dong; Xing, Wen-Min; Chen, Jie 2014-01-01 Acyclovir (ACV) is an effective and widely used antiviral agent. However, its clinical application is limited by severe nephrotoxicity. We assessed ACV-induced nephrotoxicity and identified the differentially expressed proteins using mass spectrometry-based proteomic analysis. In total, 30 ICR mice were intraperitoneally administrated ACV (150 or 600 mg/kg per day) for 9 days. After administration of ACV, levels of serum creatinine and urea nitrogen increased significantly. In addition, mouse kidneys exhibited histopathological changes and reduced expression levels of vascular endothelial growth factor (VEGF) and its receptor VEGFR2. In the proteomic analysis, more than 1,000 proteins were separated by twodimensional polyacrylamide gel electrophoresis, and a total of 20 proteins were up- or down-regulated in the ACV group compared with the saline group. Among these, six proteins (MHC class II antigen, glyoxalase 1, peroxiredoxin 1, αB-crystallin, fibroblast growth factor receptor 1-IIIb, and cytochrome c oxidase subunit Vb) were identified in association with ACV-induced nephrotoxicity. These findings were confirmed by Western blotting analysis. The differential expression levels of α-BC, Prx1, Glo I and CcO Vb suggest that oxidative damage and mitochondrial injury may be involved in ACV-induced nephrotoxicity. Furthermore, VEGF and FGF may play a role in tissue repair and the restoration process following ACV nephrotoxicity. 107. In vivo application of chitosan to facilitate intestinal acyclovir absorption in rats. Science.gov (United States) Masuda, Ayumi; Goto, Yuko; Kurosaki, Yuji; Aiba, Tetsuya 2012-07-01 The effect of chitosan on the intestinal absorption of acyclovir (ACV) was evaluated in rats, and factors influencing its facilitative effect on the ACV absorption were examined. When ACV solution containing 1% chitosan with an average molecular weight of 150 kDa was administered into the upper jejunum, a significant increase in the plasma ACV concentration was observed, with the peak ACV concentration being eight times greater than that observed with the chitosan-free solution. The chitosan-free ACV solution, whose viscosity was adjusted to remain unchanged with polyethylene glycol, did not cause an increase in the plasma concentration, and neither did the chitosan-free solutions substitutionally containing low molecular cationic compounds, triethanolamine and kanamycin. When chitosan was digested with chitosanase to shorten its polycationic polysaccharide structure, chitosan subjected to 150-min digestion retained its facilitative effect on ACV absorption, but that subjected to 420-min digestion no longer caused facilitation, in which its average molecular weight was reduced to around 10 kDa. It is therefore indicated that intestinal ACV absorption can be facilitated with chitosan, and that it is necessary for chitosan to have a certain length of polycationic polysaccharide structure to exert such facilitation. 108. Antiherpetic properties of acyclovir 5'-hydrogenphosphonate and the mutation analysis of herpes virus resistant strains. Science.gov (United States) Gus'kova, Anna A; Skoblov, Mikhail Yu; Korovina, Anna N; Yasko, Maxim V; Karpenko, Inna L; Kukhanova, Marina K; Andronova, Valeria L; Galegov, George A; Skoblov, Yuri S 2009-10-01 In this study, we continued to study antiherpetic properties of acyclovir 5'-hydrogenphosphonate (Hp-ACV) in cell cultures and animal models. Hp-ACV was shown to inhibit the development of herpetic infection in mice induced by the HSV-1/L(2) strain. The compound suppressed replication of both ACV-sensitive HSV-1/L(2) and ACV-resistant HSV1/L(2)/R strains in Vero cell culture. Viral population resistant to Hp-ACV (HSV-1/L(2)/R(Hp-ACV)) was developed much slower than ACV-resistant population. The analysis of Hp-ACV-resistant clones isolated from the HSV-1/L(2)/R(Hp-ACV) population demonstrated their partial cross-resistance to ACV. The mutations determining the resistance of HSV-1 clones to Hp-ACV were partly overlapped with mutations defining ACV resistance but did not always coincide. HSV-1/L(2)/R(Hp-ACV) herpes virus thymidine kinase is shortened from the C-terminus by 100 amino acid residues in length. 109. Differential pulse voltammetric determination of acyclovir in pharmaceutical preparations using a pencil graphite electrode. Science.gov (United States) Dilgin, Didem Giray; Karakaya, Serkan 2016-06-01 In this study, a new selective and sensitive voltammetric procedure for determination of acyclovir (ACV) was proposed using a disposable electrode, pencil graphite electrode (PGE). Cyclic and differential pulse voltammograms of ACV were recorded in Britton-Robinson buffer solution containing 0.10 M KCl with pH of 4.0 at PGE. The PGE displayed a very good electrochemical behavior with significant enhancement of the peak current compared to a glassy carbon electrode (GCE). Under experimental conditions, the PGE had a linear response range from 1.0 μM to 100.0 μM ACV with a detection limit of 0.3 μM (based on 3 Sb). Relative standard deviations of 4.8 and 3.6% were obtained for five successive determinations of 10.0 and 50.0 μM ACV, respectively, which indicate acceptable repeatability. This voltammetric method was successfully applied to the direct determination of ACV in real pharmaceutical samples. The effect of various interfering compounds on the ACV peak current was studied. 110. Electrospun formulations of acyclovir, ciprofloxacin and cyanocobalamin for ocular drug delivery. Science.gov (United States) Baskakova, Alexandra; Awwad, Sahar; Jiménez, Jennifer Quirós; Gill, Hardyal; Novikov, Oleg; Khaw, Peng T; Brocchini, Steve; Zhilyakova, Elena; Williams, Gareth R 2016-04-11 Two series of fibers containing the active ingredients acyclovir, ciprofloxacin and cyanocobalamin, and combinations of these drugs, were prepared by electrospinning. One set used the hydrophilic poly(vinylpyrrolidone) (PVP) as the filament-forming polymer, while the other used the slow-dissolving poly(ε-caprolactone) (PCL). The fibers were found to have cylindrical morphologies, although there was evidence for solvent occlusion with the PVP systems and for some drug particles in the PCL materials. The active ingredients were generally present in the amorphous physical form in the case of PVP, but evidence of crystallinity was observed with PCL. The existence of intermolecular interactions between the drugs and polymers was proven using simple molecular modeling calculations. Drug release from the various fibers was tested in a validated in vitro outflow model of the eye, and the fiber formulations found to be capable of extending drug release. We thus conclude that electrospun matrices such as those prepared in this work have potential for use as intravitreal implants. Copyright © 2016 Elsevier B.V. All rights reserved. 111. Effect of purine nucleoside analogue-acyclovir on the sperm parameters and testosterone production in rats. Science.gov (United States) Movahed, Elham; Sadrkhanlou, Rajabali; Ahmadi, Abbas; Nejati, Vahid; Zamani, Zahra 2013-04-01 Acyclovir (ACV), a synthetic purine nucleoside analogue derived from guanosine, is known to be toxic to gonads and the aim of this study was to evaluate the effect of ACV on the sperm parameters and testosterone production in rat. In this experimental study, forty adult male Wistar rats (220 ± 20 g) were randomly divided into five groups (n=8 for each group). One group served as control and one group served as sham control [distilled water was intraperitoneally (i.p.) injected]. ACV was administered intraperitoneally in the drug treatment groups (4, 16 and 48 mg/kg/day) for 15 days. Eighteen days after the last injection, rats were sacrificed by CO2 inhalation. After that, cauda epididymides were removed surgically. At the end, sperm concentrations in the cauda epididymis, sperm motility, morphology, viability, chromatin quality and DNA integrity were analyzed. Serum testosterone concentrations were determined. The results showed that ACV did not affect sperm count, but decreased sperm motility and sperm viability at 16 and 48 mg/kg dose-levels. Sperm abnormalities increased at 48 mg/kg dose-level of ACV. Further, ACV significantly increases DNA damage at 16 and 48 mg/kg dose-levels and chromatin abnormality at all doses. Besides, a significant decrease in serum testosterone concentrations was observed at 16 and 48 mg/ kg doses. The present results highly support the idea that ACV induces testicular toxicity by adverse effects on the sperm parameters and serum level of testosterone in male rats. 112. Enhancement of the antiviral activity against caprine herpesvirus type 1 of Acyclovir in association with Mizoribine. Science.gov (United States) Camero, Michele; Buonavoglia, Domenico; Lucente, Maria Stella; Losurdo, Michele; Crescenzo, Giuseppe; Trerotoli, Paolo; Casalino, Elisabetta; Martella, Vito; Elia, Gabriella; Tempesta, Maria 2017-04-01 Caprine herpesvirus 1 (CpHV-1) infection in goats is responsible for genital lesions resembling the lesions induced by herpesvirus 2 in humans (HHV-2). The immunosuppressive drug Mizoribine (MIZ) is able to increase the antiviral activity of Acyclovir (ACV) against herpesvirus infections, raising interesting perspectives on new combined therapeutic strategies. In this study the anti-CpHV-1 activity in vitro of ACV alone or in combination with MIZ was evaluated. ACV (100μg/ml) displayed an antiviral effect on CpHV-1 replication. This inhibitory effect was higher when ACV (100μg/ml) was used in association with MIZ (20μg/ml). Other combinations of ACV and MIZ in various concentrations were not as effective as ACV 100μg/ml/MIZ 20μg/ml. These findings suggest that the association of ACV and MIZ is potentially useful for treatment of genital infection by herpesviruses. Copyright © 2017 Elsevier Ltd. All rights reserved. 113. A newfangled study using risk silhouette and uncertainty approximation for quantification of acyclovir in diverse formulation Institute of Scientific and Technical Information of China (English) Karan Mittal; Riddhish Patadia; Chintan Vora; Rajashree C. Mashru 2015-01-01 Risk assessment and uncertainty approximation are two major and important parameters that need to be adopted for the development of pharmaceutical process to ensure reliable results. Additionally, there is a need to switch from the traditional method validation checklist to provide a high level of assurance of method reliability to measure quality attribute of a drug product. In the present work, evaluation of risk profile, combined standard uncertainty and expanded uncertainty in the analysis of acyclovir were studied. Uncertainty was calculated using cause-effect approach, and to make it more accurately applicable a method was validated in our laboratory as per the ICH guidelines. While assessing the results of validation, the calibration model was justified by the lack of fit and Levene’s test. Risk profile represents the future applications of this method. In uncertainty the major contribution is due to sample concentration and mass. This work demonstrates the application of theoretical concepts of calibration model tests, relative bias, risk profile and uncertainty in routine methods used for analysis in pharmaceutical field. 114. The role of topical 5% acyclovir and 1% hydrocortisone cream (Xereseâ„¢) in the treatment of recurrent herpes simplex labialis. Science.gov (United States) Hull, Christopher M; Brunton, Stephen 2010-09-01 Recurrent herpes simplex labialis (HSL), also known as orofacial herpes or cold sores, is a common clinical presentation of herpes simplex virus (HSV) infection. It may manifest as painful, distressing, and cosmetically displeasing vesicles on the lips, nose, and nasal septum. Although oral or topical treatment with antiviral agents can reduce the replication of HSV-1, the primary benefits of antiviral therapies for recurrent HSL have been limited to modest reductions in healing time; they do not mitigate the accompanying immune-mediated response of the host to the virus. The addition of a topical corticosteroid to an antiviral cream has been hypothesized to improve the clinical outcome of HSL by decreasing the HSVrelated immune-mediated inflammatory skin reaction. A recently developed topical cream containing 5% acyclovir and 1% hydrocortisone (AHC) in a novel cream vehicle has been shown to be safe and effective for the early treatment of recurrent HSL in immunocompetent adult and adolescent patients. In a well-controlled clinical trial, AHC cream significantly reduced the frequency of both ulcerative and nonulcerative recurrences (ie, the prevention of vesicular HSL lesions). Treatment was well tolerated, and there was no evidence of emergence of viral resistance to acyclovir with the addition of hydrocortisone. The AHC cream significantly reduced the recurrence of ulcerative and nonulcerative HSL lesions and shortened healing time with early treatment compared with acyclovir 5% cream and vehicle (placebo) cream. Herpes simplex labialis may not typically be considered a serious medical condition; however, the importance of treating HSL should not be overlooked, considering the continuous increase of the viral pool in the general population and the potential psychological and social consequences of the condition when left untreated. 115. Transcorneal permeation of L- and D-aspartate ester prodrugs of acyclovir: delineation of passive diffusion versus transporter involvement.

Science.gov (United States) Majumdar, Soumyajit; Hingorani, Tushar; Srirangam, Ramesh; Gadepalli, Rama Sarma; Rimoldi, John M; Repka, Michael A 2009-05-01 The aim of this study was to evaluate the contribution of amino acid transporters in the transcorneal permeation of the aspartate (Asp) ester acyclovir (ACV) prodrug. Physicochemical characterization, solubility and stability of acyclovir L-aspartate (L-Asp-ACV) and acyclovir D-aspartate (D-Asp-ACV) were studied. Transcorneal permeability was evaluated across excised rabbit cornea. Solubility of L-Asp-ACV and D-Asp-ACV were about twofold higher than that of ACV. The prodrugs demonstrated greater stability under acidic conditions. Calculated pK(a) and logP values for both prodrugs were identical. Transcorneal permeability of L-Asp-ACV (12.1 +/- 1.48 x 10(-6) cm/s) was fourfold higher than D-Asp-ACV (3.12 +/- 0.36 x 10(-6) cm/s) and ACV (3.25 +/- 0.56 x 10(-6) cm/s). ACV generation during the transport process was minimal. L-Asp-ACV transport was sodium and energy dependent but was not inhibited by glutamic acid. Addition of BCH, a specific B(0,+) and L amino acid transporter inhibitor, decreased transcorneal L-Asp-ACV permeability to 2.66 +/- 0.21 x 10(-6) cm/s. L-Asp-ACV and D-Asp-ACV did not demonstrate significant difference in stability in ocular tissue homogenates. The results demonstrate that enhanced transport of L-Asp-ACV is as a result of corneal transporter involvement (probably amino acid transporter B(0,+)) and not as a result of changes in physicochemical properties due to prodrug derivatization (permeability of D-Asp-ACV and ACV were not significantly different). 116. Phosphoramidate derivatives of acyclovir: synthesis and antiviral activity in HIV-1 and HSV-1 models in vitro. Science.gov (United States) Zakirova, Natalia F; Shipitsyn, Alexander V; Jasko, Maxim V; Prokofjeva, Maria M; Andronova, Valeria L; Galegov, Georgiy A; Prassolov, Vladimir S; Kochetkov, Sergey N 2012-10-01 The antiviral activity against HIV and HSV and the chemical stability of ACV phosphoramidate derivatives were studied. The phosphoramidates of ACV demonstrated moderate activity. The best compound appeared to be 9-(2-hydroxymethyl)guanine phosphoromonomorpholidate (7), which inhibited virus replication in pseudo-HIV-1 particles by 50% at 50 μM. It also inhibited replication of wild-type HSV-1 (9.7 μM) as well as an acyclovir-resistant strain (25 μM). None of the synthesised compounds showed any cytotoxicity. 117. A comparison of the physicochemical properties and a sensory test of Acyclovir creams. Science.gov (United States) Inoue, Yutaka; Furuya, Kayoko; Matumoto, Miruto; Murata, Isamu; Kimura, Masayuki; Kanamoto, Ikuo 2012-10-15 In external medicine, types and ratios of additives are not necessarily the same for well-known brand-name drugs and generic drugs. This study sought to compare the physicochemical properties and sensory test results of a brand-name Acyclovir (ACV) cream and two generic ACV creams. Near-infrared (NIR) spectroscopy revealed changes in absorption spectra attributed to differences in the oil and water content of the 3 creams. In addition, ACV-B and ACV-C had similar NIR absorption spectra. Microscopic examination revealed crystallization in each of the creams and droplets in ACV-C. Powder X-ray diffraction measurement revealed diffraction peaks due to ACV for ACV-A and ACV-B. Assessment of viscoelasticity indicated that stress of subjection to 35 °C caused no changes in the viscoelasticity of ACV-B and ACV-C in comparison to stress of subjection to 25 °C but it did cause the viscoelasticity of ACV-A to decrease. ACV-A had a greater tolerance to stress and a higher viscosity, tan δ, and yield value than the other 2 creams. Results of a sensory test revealed significant differences in adhesiveness, spreadability, and feel for ACV-A in comparison to ACV-B and ACV-C. Thus, differences in the viscosity and elasticity of the creams due to differences in types and ratios of additives were noted. These differences are surmised to be differences in physical properties. In addition, results suggested that viscoelasticity and spreadability in the sensory test reflected differences in physical properties. 118. Prevalence of Intrathecal Acyclovir Resistant Virus in Herpes Simplex Encephalitis Patients Science.gov (United States) Mitterreiter, Johanna G.; Titulaer, Maarten J.; van Nierop, Gijsbert P.; van Kampen, Jeroen J. A.; Aron, Georgina I.; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.; Ouwendijk, Werner J. D. 2016-01-01 Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR–associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions. Clinical samples were obtained from 12 HSE patients, encompassing 4 HSV type 1 (HSV-1) and 8 HSV-2 encephalitis patients. HSV DNA load was determined by real-time PCR and complete HSV TK gene sequences were obtained by nested PCR followed by Sanger sequencing. All HSV-1 HSE patients contained viral TK mutations encompassing 30 unique nucleotide and 13 distinct amino acid mutations. By contrast, a total of 5 unique nucleotide and 4 distinct amino acid changes were detected in 7 of 8 HSV-2 patients. Detected mutations were identified as natural polymorphisms located in non-conserved HSV TK gene regions. ACV therapy did not induce the emergence of ACVR-associated HSV TK mutations in consecutive CSF and mucocutaneous samples of 5 individual patients. Phenotypic susceptibility analysis of these mucocutaneous HSV isolates demonstrated ACV-sensitive virus in 2 HSV-1 HSE patients, whereas in two HSV-2 HSE patients ACVR virus was detected in the absence of known ACVR-associated TK mutations. In conclusion, we did not detect intrathecal ACVR-associated TK mutations in HSV isolates obtained from 12 HSE patients. PMID:27171421 119. Assessment of the physical properties and stability of mixtures of tetracycline hydrochloride ointment and acyclovir cream. Science.gov (United States) Inoue, Yutaka; Furuya, Kayoko; Maeda, Rikimaru; Murata, Isamu; Kanamoto, Ikuo 2013-04-15 In dermatology, ointments are often mixed as part of drug therapy, but mixing often leads to incompatibility. Three combinations of tetracycline ointment (TC-o) and acyclovir cream (ACV-cr) were prepared at a TC-o:ACV-cr ratio of 1:1 using a brand-name ACV-cr and two generic ACV-cr (samples TC-o+ACV-A, TC-o+ACV-B, and TC-o+ACV-C). Microscopic examination revealed separation in TC-o+ACV-C. Viscosity and elasticity measurement indicated that the storage modulus (G') and loss modulus (G″) of each of the TC-o+ACV-cr mixtures behaved similarly to those of an ACV-cr and the loss tangent (tanδ) behaved similarly to that of a TC ointment. In addition, differences in the storage modulus (G') and loss modulus (G″) of the TC-o+ACV-cr mixtures were noted. To assess stability, each TC-o+ACV-cr mixture was stored away from direct sunlight at 25 °C and an RH of 84% and at 4 °C (in a refrigerator). HPLC revealed that the ACV content in each TC-o+ACV-cr mixture remained at 95-105% for up to 14 days under both sets of storage conditions. A decline in TC content in each TC-o+ACV-cr mixture was not noted with storage at 4 °C but was noted over time with storage at 25 °C and an RH of 84%. In addition, significant differences in the percent decline in TC content in each TC-o+ACV-cr mixture occurred with storage at 25 °C and an RH of 84%. Thus, differences in physical properties and stability may occur when combining brand-name and generic drugs, and temperature and humidity may be the cause of the TC-o's incompatibility. 120. The antiviral drug acyclovir is a slow-binding inhibitor of (D)-amino acid oxidase. Science.gov (United States) Katane, Masumi; Matsuda, Satsuki; Saitoh, Yasuaki; Sekine, Masae; Furuchi, Takemitsu; Koyama, Nobuhiro; Nakagome, Izumi; Tomoda, Hiroshi; Hirono, Shuichi; Homma, Hiroshi 2013-08-20 d-Amino acid oxidase (DAO) is a degradative enzyme that is stereospecific for d-amino acids, including d-serine and d-alanine, which are believed to be coagonists of the N-methyld-aspartate (NMDA) receptor. To identify a new class of DAO inhibitor(s) that can be used to elucidate the molecular details of the active site environment of DAO, manifold biologically active compounds of microbial origin and pre-existing drugs were screened for their ability to inhibit DAO activity, and several compounds were identified as candidates. One of these compounds, acyclovir (ACV), a well-known antiviral drug used for the treatment of herpesvirus infections, was characterized and evaluated as a novel DAO inhibitor in vitro. Analysis showed that ACV acts on DAO as a reversible slow-binding inhibitor, and interestingly, the time required to achieve equilibrium between DAO, ACV, and the DAO/ACV complex was highly dependent on temperature. The binding mechanism of ACV to DAO was investigated in detail by several approaches, including kinetic analysis, structural modeling of DAO complexed with ACV, and site-specific mutagenesis of an active site residue postulated to be involved in the binding of ACV. The results confirm that ACV is a novel, active site-directed inhibitor of DAO that can be a valuable tool for investigating the structure-function relationships of DAO, including the molecular details of the active site environment of DAO. In particular, it appears that ACV can serve as an active site probe to study the structural basis of temperature-induced conformational changes of DAO. « 4 5 6 7 8 » « 5 6 7 8 9 » 121. Prevalence of Intrathecal Acyclovir Resistant Virus in Herpes Simplex Encephalitis Patients. Science.gov (United States) Mitterreiter, Johanna G; Titulaer, Maarten J; van Nierop, Gijsbert P; van Kampen, Jeroen J A; Aron, Georgina I; Osterhaus, Albert D M E; Verjans, Georges M G M; Ouwendijk, Werner J D 2016-01-01 Herpes simplex encephalitis (HSE) is a life-threatening complication of herpes simplex virus (HSV) infection. Acyclovir (ACV) is the antiviral treatment of choice, but may lead to emergence of ACV-resistant (ACVR) HSV due to mutations in the viral UL23 gene encoding for the ACV-targeted thymidine kinase (TK) protein. Here, we determined the prevalence of intrathecal ACVR-associated HSV TK mutations in HSE patients and compared TK genotypes of sequential HSV isolates in paired cerebrospinal fluid (CSF) and blister fluid of mucosal HSV lesions. Clinical samples were obtained from 12 HSE patients, encompassing 4 HSV type 1 (HSV-1) and 8 HSV-2 encephalitis patients. HSV DNA load was determined by real-time PCR and complete HSV TK gene sequences were obtained by nested PCR followed by Sanger sequencing. All HSV-1 HSE patients contained viral TK mutations encompassing 30 unique nucleotide and 13 distinct amino acid mutations. By contrast, a total of 5 unique nucleotide and 4 distinct amino acid changes were detected in 7 of 8 HSV-2 patients. Detected mutations were identified as natural polymorphisms located in non-conserved HSV TK gene regions. ACV therapy did not induce the emergence of ACVR-associated HSV TK mutations in consecutive CSF and mucocutaneous samples of 5 individual patients. Phenotypic susceptibility analysis of these mucocutaneous HSV isolates demonstrated ACV-sensitive virus in 2 HSV-1 HSE patients, whereas in two HSV-2 HSE patients ACVR virus was detected in the absence of known ACVR-associated TK mutations. In conclusion, we did not detect intrathecal ACVR-associated TK mutations in HSV isolates obtained from 12 HSE patients. 122. Identification and characterization of acyclovir-resistant clinical HSV-1 isolates from children. Science.gov (United States) Wang, Yi; Wang, Qi; Zhu, Qinchang; Zhou, Rong; Liu, Jinsong; Peng, Tao 2011-10-01 The occurrence of herpes simplex virus (HSV) with acyclovir (ACV) resistance is a cause for concern due to the frequent use of ACV for treatment, suppressive therapy, and prophylaxis of HSV infection. Although HSV infection is prevalent among children, very little is known about the drug susceptibility of HSV circulating in this patient population. To determine the status of ACV resistant HSV-1 among children. A reporter cell-based HSV infection assay (mVILA) was developed to conveniently evaluate the ACV susceptibility of HSV-1 clinical strains and used to analyze 68 HSV-1 primary isolates from oral lesions in children. Compared with PRA, mVILA is easier to perform. Using mVILA, HSV-1 isolates C106, C153, and C174 were found completely resistant to ACV, with a greater than 100-fold increase in IC50s. Sequence analysis of thymidine kinase (TK) and DNA polymerase (DNA POL) genes identified 11 new mutations. Structural modeling of the TK and DNA POL proteins suggested structural changes that might alter their interactions with ACV and ACV triphosphate, respectively. The insertion of a single G in a seven-guanine homopolymeric repeat sequence generated a truncated TK protein in C106. This study provides preliminary data on the ACV susceptibility status of HSV-1 in children. The prevalence rate of ACV-resistant HSV-1 in children was higher than predicted. Moreover, multiple mechanisms leading to the resistance were identified. These results suggest that new anti-herpetics with different working mechanisms should be valuable. Copyright © 2011 Elsevier B.V. All rights reserved. 123. An investigative peptide-acyclovir combination to control herpes simplex virus type 1 ocular infection. Science.gov (United States) Park, Paul J; Antoine, Thessicar E; Farooq, Asim V; Valyi-Nagy, Tibor; Shukla, Deepak 2013-09-27 To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection. The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR. Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti-HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV-treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection. This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection. 124. An Investigative Peptide–Acyclovir Combination to Control Herpes Simplex Virus Type 1 Ocular Infection Science.gov (United States) Park, Paul J.; Antoine, Thessicar E.; Farooq, Asim V.; Valyi-Nagy, Tibor; Shukla, Deepak 2013-01-01 Purpose. To investigate the efficacy of a combination treatment composed of the cationic, membrane-penetrating peptide G2, and acyclovir (ACV) in both in vitro and ex vivo models of herpes simplex virus 1 (HSV-1) ocular infection. Methods. The antiviral activity of a combined G2 peptide and ACV therapy (G2-ACV) was assessed in various treatment models. Viral entry, spread, and plaque assays were performed in vitro to assess the prophylactic efficacy of G2, G2-ACV, and ACV treatments. In the ex vivo model of HSV-1 infection, the level of viral inhibition was also compared among the three treatment groups via Western blot analysis and immunohistochemistry. The potential change in expression of the target receptor for G2 was also assessed using immunohistochemistry and RT-PCR. Results. Statistically significant effects against HSV-1 infection were seen in all treatment groups in the viral entry, spread, and plaque assays. The greatest effects against HSV-1 infection in vitro were seen in the G2-ACV group. In the ex vivo model, statistically significant anti–HSV-1 effects were also noted in all control groups. At 24 hours, the greatest inhibitory effect against HSV-1 infection was seen in the ACV group. At 48 hours, however, the G2-ACV–treated group demonstrated the greatest antiviral activity. Syndecan-1, a target of G2, was found to be upregulated at 12-hours postinfection. Conclusions. This study shows that G2-ACV may be an effective antiviral against HSV-1 (KOS) strain when applied as single prophylactic applications with or without continuous doses postinfection. PMID:23989188 125. Genotypic detection of acyclovir-resistant HSV-1: characterization of 67 ACV-sensitive and 14 ACV-resistant viruses. Science.gov (United States) Frobert, Emilie; Cortay, Jean-Claude; Ooka, Tadamasa; Najioullah, Fatiha; Thouvenot, Danielle; Lina, Bruno; Morfin, Florence 2008-07-01 Infections due to herpes simplex virus (HSV) resistant to acyclovir (ACV) represent an important clinical concern in immunocompromised patients. In order to switch promptly to an appropriate treatment, rapid viral susceptibility assays are required. We developed herein a genotyping analysis focusing on thymidine kinase gene (TK) mutations in order to detect acyclovir-resistant HSV in clinical specimens. A total of 85 HSV-1 positive specimens collected from 69 patients were analyzed. TK gene could be sequenced directly for 81 clinical specimens (95%) and 68 HSV-1 specimens could be characterized as sensitive or resistant by genotyping (84%). Genetic characterization of 67 susceptible HSV-1 specimens revealed 10 polymorphisms never previously described. Genetic characterization of 14 resistant HSV-1 revealed 12 HSV-1 with either TK gene additions/deletions (8 strains) or substitutions (4 strains) and 2 HSV-1 with no mutation in the TK gene. DNA polymerase gene was afterwards explored. With this rapid PCR-based assay, ACV-resistant HSV could be detected directly in clinical specimens within 24 h. 126. Novel water-soluble prodrugs of acyclovir cleavable by the dipeptidyl-peptidase IV (DPP IV/CD26) enzyme. Science.gov (United States) Diez-Torrubia, Alberto; Cabrera, Silvia; de Castro, Sonia; GarcÃa-Aparicio, Carlos; Mulder, Gwenn; De Meester, Ingrid; Camarasa, MarÃa-José; Balzarini, Jan; Velázquez, Sonsoles 2013-01-01 We herein report for the first time the successful use of the dipeptidyl peptidase IV (DPPIV/CD26) prodrug approach to guanine derivatives such as the antiviral acyclovir (ACV). The solution- and solid-phase synthesis of the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of acyclovir are reported. The synthesis of the demanding tetrapeptide amide prodrug of ACV 3 was first established in solution and successfully transferred onto solid support by using Ellman's dihydropyran (DHP) resin. In contrast with the valyl ester prodrug (valacyclovir, VACV), the tetrapeptide amide prodrug 3 and the tripeptide ester conjugate 4 of ACV proved fully stable in PBS. Both prodrugs converted to VACV (for 4) or ACV (for 3) upon exposure to purified DPPIV/CD26 or human or bovine serum. Vildagliptin, a potent inhibitor of DPPIV/CD26 efficiently inhibited the DPPIV/CD26-catalysed hydrolysis reaction. Both amide and ester prodrugs of ACV showed pronounced anti-herpetic activity in cell culture and significantly improved the water solubility in comparison with the parent drug. 127. Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus Infections In Vitro Directory of Open Access Journals (Sweden) Carol L. Berkower 2013-01-01 Full Text Available Following initial infection, herpesviruses retreat into a permanent latent state with periodic reactivation resulting in an enhanced likelihood of transmission and clinical disease. The nucleoside analogue acyclovir reduces clinical symptoms of the three human alpha herpesviruses, HSV-1, HSV-2, and VZV. Long-term administration of acyclovir (ACV can reduce the frequency and severity of reactivation, but its low bioavailability and short half-life require a daily drug regimen. Our lab is working to develop a subcutaneous delivery system to provide long-lasting, sustained release of ACV. Previously, we demonstrated that an implantable silicone (MED-4050 device, impregnated with ACV protected against HSV-1 both in vitro and in vivo. Here, we extend our in vitro observations to include protection against both HSV-2 and VZV. We also demonstrate protection against HSV-2 in vitro using MED-4750, a silicone polymer designed for long-term use in humans. When release of ACV from MED-4750 is quantitated on a daily basis, an initial burst of 5 days is observed, followed by a long period of slow release with near-zero-order kinetics, with an average daily release of 1.3923 ± 0.5908 μg ACV over days 20–60. Development of a slow-release implant has the potential to significantly impact the treatment of human alpha herpesvirus infections. 128. Preparation and evaluation of novel in situ gels containing acyclovir for the treatment of oral herpes simplex virus infections. Science.gov (United States) Chaudhary, Binu; Verma, Surajpal 2014-01-01 The objective of this work was to develop an oral mucosal drug delivery system to facilitate the local and systemic delivery of acyclovir for the treatment of oral herpes infection caused by the herpes simplex virus (HSV). An in situ gelling system was used to increase the residence time and thus the bioavailability of acyclovir in oral mucosa. Temperature and pH trigged in situ gel formulations were prepared by cold method using polymers like poloxamer 407, carbopol 934, and HPMC. Glycerin and a mixture of tween 80 and ethanol (1â €‰: 2 ratio) were used as the drug dissolving solvent. The pH of carbopol containing formulation was adjusted to pH 5.8 while the pH of poloxamer solution was adjusted to pH 7. These formulations were evaluated for sol-gel transition temperature, gelling capacity, pH, viscosity, spreadability, gel strength, drug content, ex-vitro permeation, and mucoadhesion. The gelation temperatures of all the formulations were within the range of 28-38°C. All the formulations exhibited fairly uniform drug content (98.15-99.75%). Drug release study of all the formulations showed sustained release properties. The release of drug through these in situ gel formulations followed the Higuchi model and Korsmeyer peppas model mechanism. 129. Recent approval of Xerese in Canada: 5% acyclovir and 1% hydrocortisone topical cream in the treatment of herpes labialis. Science.gov (United States) Nguyen, H P; Stiegel, K R; Downing, C; Stiegel, K R 2014-01-01 Herpes labialis is a frequently occurring viral infection of the lips and oral mucosa. Recurring lesions are induced by viral reactivation and replication, but the symptoms leading to morbidity, such as pain and inflammation, are immune-mediated. The introduction of 5% acyclovir/1% hydrocortisone in a topical cream (Xereseâ„¢) represents a therapeutic strategy directed at both of these pathogenic processes. Applied at the onset of prodromal symptoms, this combination treatment has a good safety profile and is more effective in reducing healing time than antiviral or anti-inflammatory agents alone. Although it was US FDA-approved for herpes labialis in 2009, Xereseâ„¢ has only recently been approved for use in Canada in October 2013. Herein, we review the basic science and clinical studies that support the efficacy of this topical combination acyclovir-hydrocortisone product in treating herpes labialis and examine its safety profile, as well as touch upon other therapies that have been shown to be effective in treating this common viral condition. 130. Influence of drug loading and type of ointment base on the in vitro performance of acyclovir ophthalmic ointment. Science.gov (United States) Al-Ghabeish, Manar; Xu, Xiaoming; Krishnaiah, Yellela S R; Rahman, Ziyaur; Yang, Yang; Khan, Mansoor A 2015-11-30 The availability of in vitro performance tests such as in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) are critical to comprehensively assure consistent delivery of the active component(s) from semisolid ophthalmic drug products. The objective was to study the impact of drug loading and type of ointment base on the in vitro performance (IVRT and IVPT) of ophthalmic ointments using acyclovir as a model drug candidate. The in vitro drug release for the ointments was evaluated using a modified USP apparatus 2 with Enhancer cells. The transcorneal permeation was carried out using rabbit cornea on modified vertical Franz cells. The drug retention in cornea (DRC) was also determined at the end of transcorneal drug permeation study. The in vitro drug release, transcorneal drug permeation as well as DRC exhibited a proportional increase with increasing drug loading in the ointment. On comparing the in vitro drug release profile with transcorneal permeation profile, it appears that drug release from the ointment is controlling acyclovir transport through the cornea. Furthermore, enhanced in vitro transcorneal permeation relative to the in vitro drug release underscores the importance of the interplay between the physiology of the ocular tissue and ointment formulation. The results indicated that IVRT and IVPT could be used to discriminate the impact of changes in drug load and formulation composition of ophthalmic ointments. 131. Evaluation of sorivudine (BV-araU) versus acyclovir in the treatment of acute localized herpes zoster in human immunodeficiency virus-infected adults NARCIS (Netherlands) Bodsworth, NJ; Boag, F; Burdge, D; Genereux, M; Borleffs, JCC; Evans, BA; Modai, J; Colebunders, R; Thomas, M; DeHertogh, D; Pacelli, L; Thomis, J; Knight, E.L.; McNulty, AM; Delaney, C; VanHove, D; Sacks, S; Gage, L; McLeod, A; DiazMitoma, F; Fong, J; MacFadden, D; Martel, A; Rachlis, A; Salit, [No Value; Shafran, S; Szabo, J; Toma, E; Deschenes, L; Gill, J; Lalonde, R; Kaufhold, R; Molina, JM; Dellamonica, P; Rozenbaum, W; Kolsters, FP; Meenhorst, PL; Danner, S; Sprenger, HG; EllisPegler, RB; Moragas, J; Moyle, G; Colman, J; Parnell, A; McLean, KA; Holmes, DA; Kitchen, C.M.R.; Linde, A; Dahl, H; Dwyer, D 1997-01-01 The clinical efficacy and safety of sorivudine as treatment for acute cutaneous tester in human immunodeficiency virus-infected adults was compared with that of acyclovir in a double-blinded randomized study, A total of 125 patients with laboratory-confirmed tester rash present for less than or equa 132. Randomized clinical study comparing Compeed (R) cold sore patch to acyclovir cream 5% in the treatment of herpes simplex labialis DEFF Research Database (Denmark) Karlsmark, T.; Goodman, J.J.; Drouault, Y. 2008-01-01 Background Hydrocolloid technology has been proven effective in treating dermal wounds. A previous study showed that a newly developed thin hydrocolloid patch [Compeed (R) cold sore patch (CSP)] provided multiple wound-healing benefits across all stages of a herpes simplex labialis (HSL) outbreak......) at the onset of symptoms until the lesion healed, for a maximum of 10 days. The primary end point was the subject's global assessment of therapy (SGAT; 0-10 scale; 0 = no response, 10 = excellent response). Multiple secondary end points included clinician-assessed healing time and subject assessment of lesion...... protection, noticeability and social embarrassment. Results CSP and acyclovir were highly

effective (mean SGAT = 7.89 and 8.00, respectively), with no significant difference observed (P = 0.65). The difference in healing times between products was not significant (median, 7.57 days with CSP vs. 7.03 days... 133. Efficacy of Topical 5% Acyclovir-1% Hydrocortisone Cream (ME-609 for Treatment of Herpes Labialis: a systematic review Directory of Open Access Journals (Sweden) MARIA INÊS DA ROSA 2015-08-01 Full Text Available We performed a systematic review with the objective of verifying the efficacy of topical use 5% Acyclovir-1% Hydrocortisone cream compared to the placebo group for herpes simplex labialis treatment. We performed a literature search using MEDLINE, Embase, BIOSIS, LILACS, Scopus, Grey literature, the Cochrane Central Register of Controlled Trials, the ISI Web of Science and IBECS from 1990 to June 2014. We reported the outcomes using relative risk (RR with 95% confidence intervals. The literature search yielded 180 potentially relevant publications. Reviews of the reference lists yielded two further citations. Among these papers, two were considered eligible for inclusion in this review. Both trials included 1,213 patients. A meta-analysis of these studies showed a RR = 0.77, (95% CI 0.70-0.86; p30 DU/L and ACV-resistant isolates have activity values ACV-resistant HSV-1 isolates can have TK activity values >30 DU/L. These strains are most likely ACV-resistant TK-altered mutants, but no evidence was provided for an alteration of the TK. 136. Absence of rapid selection for acyclovir or penciclovir resistance following suboptimal oral prodrug therapy of HSV-infected mice Directory of Open Access Journals (Sweden) Bacon Teresa H 2001-12-01 Full Text Available Abstract Background Acyclovir (ACV resistant herpes simplex virus (HSV isolates can be readily selected in animal infection models receiving suboptimal ACV treatment, however no comparative studies of the emergence of resistance following suboptimal treatment with valacyclovir (VCV or famciclovir (FCV, the prodrugs of acyclovir and penciclovir, respectively, have been reported. Methods Mice (n = 30 were infected with HSV type 1 or 2 in the ear pinnae and administered oral prodrugs at one fifth a dose previously shown to be effective. To select and amplify drug-resistant HSV, a total of seven consecutive in vivo passages with suboptimal treatment were performed for each virus sample and progeny virus from each passage was characterized by the plaque reduction (PRA and plating efficiency assays (PEA. Results No drug-resistant HSV-2 and only a single drug-resistant HSV-1 variant were identified. Virus recovered from the first three sequential passages of this HSV-1 sample was susceptible by PRA, although the proportion of resistant virus recovered gradually increased upon passage. The resistant HSV-1 phenotype was confirmed by PRA after four sequential passages in mice. Unexpectedly, this in vivo-selected drug-resistant HSV-1 failed to yield an infection completely refractory to treatment in subsequent passages. Conclusions Sub-optimal therapy of immunocompetent mice with either VCV or FCV did not readily select for HSV-mutants resistant to either ACV or PCV, suggesting that selection of resistance with either prodrug remains difficult using this system. Futhermore, this study suggests that the PEA may represent a useful adjunct to the PRA for monitoring alterations in the proportion of drug-resistant virus even when no change in IC50 is apparent. 137. Successful clearance of cutaneous acyclovir-resistant, foscarnet-refractory herpes virus lesions with topical cidofovir in an allogeneic hematopoietic stem cell transplant patient. Science.gov (United States) Muluneh, B; Dean, A; Armistead, P; Khan, T 2013-06-01 Cidofovir is a deoxycytidine monophosphate analog with broad spectrum activity against various deoxyribonucleic acid viruses. Cidofovir is marketed as an injectable for intravenous use; however, there is a topical cidofovir formulation utilized for viral dermatologic infections. Here, we present a case of a successful clearance of a perianal acyclovir resistant and foscarnet refractory herpes simplex virus (HSV1) ulcer in a 34 year-old woman who had undergone allogeneic hematopoietic stem cell transplantation. After 1 week of therapy with cidofovir gel, the patient's ulcer was clinically improved, and the lesion was negative for herpes simplex virus transcripts by real-time polymerase chain reaction testing. The wound remained herpes simplex virus negative by real-time polymerase chain reaction on repeat testing 1 week later. Based on this and other reports in HIV/AIDS patients, we believe that cidofovir gel has utility in the management of cutaneous, acyclovir-resistant HSV infections. 138. A comparative study of lamellar gel phase systems and emzaloids as transdermal drug delivery systems for acyclovir and methotrexate / Sonique Reynecke OpenAIRE Reynecke, Sonique 2004-01-01 The skin forms an attractive and accessible route for systemic delivery of drugs as alternative to other methods of administration, such as the oral and parental methods because of the problems associated with last mentioned methods. The lipophilic character of the stratum corneum, coupled with its intrinsic tortuosity, ensures that it almost always provides the principal barrier to the entry of drug molecules into the skin. Due to the fact that methotrexate (MTX) and acyclovir... 139. Utilization of nanotechnology to enhance percutaneous absorption of acyclovir in the treatment of herpes simplex viral infections Directory of Open Access Journals (Sweden) Al-Subaie MM 2015-06-01 Full Text Available Mutlaq M Al-Subaie,1 Khaled M Hosny,1,2 Khalid Mohamed El-Say,1,3 Tarek A Ahmed,1,3 Bader M Aljaeid1 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, 3Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt Abstract: This study aimed to formulate an optimized acyclovir (ACV nanoemulsion hydrogel in order to provide a solution for the slow, variable, and incomplete oral drug absorption in patient suffering from herpes simplex viral infection. Solubility of ACV in different oils, surfactants, and cosurfactants was explored utilizing a cubic model mixture design to obtain a nanoemulsion with minimum globule size. Preparation of an optimized ACV nanoemulsion hydrogel using a three-factor, three-level Box–Behnken statistical design was conducted. The molecular weight of chitosan (X1, percentage of chitosan (X2, and percentage of Eugenol as a skin permeation enhancer (X3 were selected to study their effects on hydrogel spreadability (Y1 and percent ACV permeated through rat skin after 2.5 hours (Y2. A pharmacokinetic study of the optimized ACV nanoemulsion hydrogel was conducted in rats. Mixtures of clove oil and castor oil (3:1 ratio, Tween 80 and Span 80 (3:1 ratio, and propylene glycol and Myo-6V (3:1 ratio were selected as the oil, surfactant, and cosurfactant phases, respectively. Statistical analysis indicated that the molecular weight of chitosan has a significant antagonistic effect on spreadability, but has no significant effect on the percent ACV permeated. The percentage of chitosan also has a significant antagonistic effect on the spreadability and percent ACV permeated. On the other hand, the percentage of Eugenol has a significant synergistic effect on percent ACV permeated, with no effect on 140. Mechanisms associated with HIV-1 resistance to acyclovir by the V75I mutation in reverse transcriptase. Science.gov (United States) Tchesnokov, Egor P; Obikhod, Aleksandr; Massud, Ivana; Lisco, Andrea; Vanpouille, Christophe; Brichacek, Beda; Balzarini, Jan; McGuigan, Christopher; Derudas, Marco; Margolis, Leonid; Schinazi, Raymond F; Götte, Matthias 2009-08-01 It has recently been demonstrated that the anti-herpetic drug acyclovir (ACV) also displays antiviral activity against the human immunodeficiency virus type 1 (HIV-1). The triphosphate form of ACV is accepted by HIV-1 reverse transcriptase (RT), and subsequent incorporation leads to classical chain termination. Like all approved nucleoside analogue RT inhibitors (NRTIs), the selective pressure of ACV is associated with the emergence of resistance. The V75I mutation in HIV-1 RT appears to be dominant in this regard. By itself, this mutation is usually not associated with resistance to currently approved NRTIs. Here we studied the underlying biochemical mechanism. We demonstrate that V75I is also selected under the selective pressure of a monophosphorylated prodrug that was designed to bypass the bottleneck in drug activation to the triphosphate form (ACV-TP). Pre-steadystate kinetics reveal that V75I discriminates against the inhibitor at the level of catalysis, whereas binding of the inhibitor remains largely unaffected. The incorporated ACVmonophosphate (ACV-MP) is vulnerable to excision in the presence of the pyrophosphate donor ATP. V75I compromises binding of the next nucleotide that can otherwise provide a certain degree of protection from excision. Collectively, the results of this study suggest that ACV is sensitive to two different resistance pathways, which warrants further investigation regarding the detailed resistance profile of ACV. Such studies will be crucial in assessing the potential clinical utility of ACV and its derivatives in combination with established NRTIs. « 5 6 7 8 9 » « 6 7 8 9 10 » 141. Resistance of herpes simplex viruses to acyclovir: an update from a ten-year survey in France. Science.gov (United States) Frobert, Emilie; Burrel, Sonia; Ducastelle-Lepretre, Sophie; Billaud, Geneviève; Ader, Florence; Casalegno, Jean-Sébastien; Nave, Viviane; Boutolleau, David; Michallet, Mauricette; Lina, Bruno; Morfin, Florence 2014-11-01 The widespread use of acyclovir (ACV) and the increasing number of immunocompromised patients have raised concern about an increase in ACV-resistant herpes simplex virus (HSV). ACV resistance has traditionally been a major concern for immunocompromised patients with a frequency reported between 2.5% and 10%. The aim of this study was to reassess the status of HSV resistance to ACV in immunocompetent and immunocompromised patients over a ten year period, between 2002 and 2011. This was done by retrospectively following 1425 patients. In immunocompetent patients, prevalence of resistance did not exceed 0.5% during the study period; whereas in immunocompromised patients, a significant increase was observed, rising from 3.8% between 2002 and 2006 (7/182 patients) to 15.7% between 2007 and 2011 (28/178) (p=0.0001). This sharp rise in resistance may largely be represented by allogeneic hematopoietic stem cell transplant patients, in which the prevalence of ACV resistance rose similarly from 14.3% (4/28) between 2002 and 2006 to 46.5% (26/56) between 2007 and 2011 (p=0.005). No increase in ACV resistance was detected in association with other types of immune deficiencies. Genotypic characterization of HSV UL23 thymidine kinase and UL30 DNA polymerase genes revealed 11 and 7 previously unreported substitutions, respectively. These substitutions may be related to potential polymorphisms, drug resistance, or other mutations of unclear significance. 142. A metabolic profiling analysis of the nephrotoxicity of acyclovir in rats using ultra performance liquid chromatography/mass spectrometry. Science.gov (United States) Xing, Wenmin; Gu, Lili; Zhang, Xinyue; Xu, Jiadong; Lu, Hong 2016-09-01 Acyclovir (ACV) exposure is a common cause of acute kidney injury (AKI). The toxicity mechanism of ACV has always been a matter of debate. The present study investigated into the time-effect relationship and dose-effect relationship of ACV-induced nephrotoxicity in rats using metabonomics. Twenty-four rats were randomly divided into four groups: a 0.9% NaCl solution group, and 100, 300, and 600mg/kg ACV-treated groups; the ACV or vehicle solution was administered with a single intravenous injection. Urine was collected at different time periods (12h before administration, and 0-6h, 7-12h, and 13-24h after administration). Routine urinalysis was conducted by a urine automatic analyzer. Renal markers, including urine urea nitrogen, urine creatinine, and urinary N-acetyl-β-d-glucosaminidase (NAG) activity, were determined using established protocols. Urinary metabolites were evaluated using ultra performance liquid chromatography/mass spectrometry (UPLC/MS). In the ACV-treated rats, increased levels of protein (PRO), occult blood (BLD), white blood cell (WBC), and NAG activity in urine were observed, while the urine creatinine and urea nitrogen levels showed a decrease compared with the control. Moreover, urine metabolites significantly changed after the treatment with ACV, and all the effects induced by ACV were dose-time dependent. Finally, 4 metabolites (guanine, 4-guanidinobutyric acid, creatinine, and urea) were identified, which can be used for further research on the mechanism of ACV-induced nephrotoxicity. 143. Monitoring of bystander effect of herpes simplex virus thymidine kinase/acyclovir system using fluorescence resonance energy transfer technique. Science.gov (United States) Xiong, Tao; Li, Yongjun; Ni, Fenge; Zhang, Feng 2012-02-01 Cytotoxic gene therapy mediated by gene transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene followed by acyclovir (ACV) treatment has been reported to inhibit malignant tumor growth in a variety of studies. The magnitude of "bystander effect" is an essential factor for this anti-tumor approach in vivo. However, the mechanism by which HSV-tk/ACV brings "bystander effect" is poorly understood. In this report, the plasmid CD3 (ECFP-CRS-DsRed) and TK-GFP were transferred to the human adenoid cystic carcinoma line ACC-M cell line. The CD3-expressing cells apoptosis was monitored using fluorescence resonance energy transfer (FRET) technique. First, CD3 and TK-GFP coexpressing ACC-M cells apoptosis was monitored using FRET technique. The apoptosis was induced by ACV and initiated by caspase3. The FRET efficient was remarkably decreased and then disappeared during cellular apoptosis, which indicated that the TK-GFP expressing ACC-M cells apoptosis, induced by ACV, was via a caspase3-dependent pathway. Secondly, CD3 and TK-GFP mixed expressing ACC-M cells apoptosis, induced by ACV, were monitored using FRET technique. The apoptotic phenomena appeared in the CD3-expressing ACC-M cells. The results show that HSV-tk/ACV system killed ACC-M cells using its bystander effect. These results confirm that HSV-tk/ACV system is potential for cancer gene therapy. 144. Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax Using Density Functional Theory Methods Directory of Open Access Journals (Sweden) Margarita Clara Alvarez-Ros 2014-06-01 Full Text Available The five tautomers of the drug acyclovir (ACV were determined and optimised at the MP2 and B3LYP quantum chemical levels of theory. The stability of the tautomers was correlated with different parameters. On the most stable tautomer N1 was carried out a comprehensive conformational analysis, and the whole conformational parameters (R, β, Φ, φ1, φ2, φ3, φ4, φ5 were studied as well as the NBO Natural atomic charges. The calculations were carried out with full relaxation of all geometrical parameters. The search located at least 78 stable structures within 8.5 kcal/mol electronic energy range of the global minimum, and classified in two groups according to the positive or negative value of the torsional angle j1. In the nitrogen atoms and in the O2' and O5' oxygen atoms of the most stable conformer appear a higher reactivity than in the natural nucleoside deoxyguanosine. The solid state was simulated through a dimer and tetramer forms and the structural parameters were compared with the X-ray crystal data available. Several general conclusions were emphasized. 145. Impact of Pluronic F-68 vs Tween 80 on Fabrication and Evaluation of Acyclovir SLNs for Skin Delivery. Science.gov (United States) Newton, Maria John; Kaur, Bhupinder 2016-07-24 The solid lipid nanoparticles (SLNs) of Acyclovir (ACV) were fabricated with Soya lecithin and Fractionated Coconut oil (medium chain glyceride) as a first time combination. The research was focused on developing ACV-SLN by using high pressure hot-homogenization technique. The ingredients were used in different concentrations and ratios to identify the best formulation design. The tween 80 and Pluronic F-68 were used in various concentrations in formulation design to assess the impact on the fabrication and evaluation of SLNs. The SLNs were subjected to various characterization techniques such as XRD ,FTIR, Master sizer analysis and zeta potential. The mean particle size was determined by master sizer and zeta sizer. Transmission electron microscopy (TEM) was used as a tool to analyze the morphology and other features. The zeta potential and drug entrapment efficiency (EE%) were also determined for the prepared ACV-SLNs. The efficiency of drug release from prepared formulations was studied by using in vitro study with the utilization of dialysis membrane technique. SLN dispersions exhibited the average size in nano range. SLNs with small particle size found to have predetermined encapsulation efficiency, and relatively high loading capacity and predetermined in vitro drug release profile. 146. In vitro evaluation of cutaneous penetration of acyclovir from semisolid commercial formulations and relation with its effective antiviral concentration Directory of Open Access Journals (Sweden) Rafaela Martins Sponchiado Full Text Available ABSTRACT The evaluation of drug permeation/penetration of semisolid formulations into animal skin can be useful to supplement the pharmaceutical equivalence. This paper describes the in vitro assessment of acyclovir (ACV into porcine skin from commercial formulations with etermination of drug concentration in different layers of cutaneous tissue to correlate with effective antiviral concentration in order to improve the equivalence decision. Studies were conducted using Franz cells and porcine skin. Selected pharmaceutical creams containing ACV had identical (reference and generic and different (similar excipients. A software program was employed for the simulation of antiviral effectiveness in the skin. Regarding ACV skin penetration, the first batch of the generic product showed a significant difference from reference and similar products, while in the second batch all products demonstrated equivalent drug penetration in the skin. Simulation studies suggest that formulations analysed exhibit a pharmacological effect even when in contact with Herpes simplex strains of high IC50 (inhibitory concentration required to reduce viral replication by 50%. According to results, it can be assumed that the in vitro cutaneous permeation/penetration study does not supply sensitivity information regarding small alterations of ACV semisolid formulations due to the variability inherent to the method, although it can be relevant to pharmaceutical equivalence studies in the development of semisolid products. 147. Novel biotinylated lipid prodrugs of acyclovir for the treatment of herpetic keratitis (HK): transporter recognition, tissue stability and antiviral activity. Science.gov (United States) Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Earla, Ravinder; Sirimulla, Suman; Bailey, Jake Brain; Pal, Dhananjay; Mitra, Ashim K 2013-08-01 Biotinylated lipid prodrugs of acyclovir (ACV) were designed to target the sodium dependent multivitamin transporter (SMVT) on the cornea to facilitate enhanced cellular absorption of ACV. All the prodrugs were screened for in vitro cellular uptake, interaction with SMVT, docking analysis, cytotoxicity, enzymatic stability and antiviral activity. Uptake of biotinylated lipid prodrugs of ACV (B-R-ACV and B-12HS-ACV) was significantly higher than biotinylated prodrug (B-ACV), lipid prodrugs (R-ACV and 12HSACV) and ACV in corneal cells. Transepithelial transport across rabbit corneas indicated the recognition of the prodrugs by SMVT. Average Vina scores obtained from docking studies further confirmed that biotinylated lipid prodrugs possess enhanced affinity towards SMVT. All the prodrugs studied did not cause any cytotoxicity and were found to be safe and non-toxic. B-R-ACV and B-12HS-ACV were found to be relatively more stable in ocular tissue homogenates and exhibited excellent antiviral activity. Biotinylated lipid prodrugs demonstrated synergistic improvement in cellular uptake due to recognition of the prodrugs by SMVT on the cornea and lipid mediated transcellular diffusion. These biotinylated lipid prodrugs appear to be promising drug candidates for the treatment of herpetic keratitis (HK) and may lower ACV resistance in patients with poor clinical response. 148. 阿昔洛韦过é‡è‡´æ€¥æ€§è‚¾è¡°ç«è¯Šæ²»åˆ†æž%Acyclovir-induced acute renal failure and a review of the literature Institute of Scientific and Technical Information of China (English) 侯欣; 王磊; 范晋海; å•æ™¶; 冯婕; è°å³° 2011-01-01 目的 探讨阿昔洛韦过é‡å¯¼è‡´æ€¥æ€§è‚¾åŠŸèƒ½è¡°ç«çš„组织å¦ç‰¹ç‚¹ã€ä¸´åºŠè¡¨çŽ°ã€æ²»ç–—以åŠé¢„åŽ.方法 报告1例阿昔洛韦过é‡å¯¼è‡´çš„æ€ ¥æ€§è‚¾åŠŸèƒ½è¡°ç«æ‚£è€…的临床ã€ç—…ç†åŠé¢„åŽèµ„æ–™,系统å¤ä¹ 相关文献进行讨论.结果 患者ä¸å¹´ç”·æ€§,å› å³ä¾§é¢ˆèƒŒéƒ¨"å¸¦çŠ¶ç–±ç– ¹"给予阿昔洛韦é™æ»´è”åˆå£æœæ²»ç–—,于æ¯æ¬¡é™æ»´åŠå°æ—¶å†…出现çªå‘è…°ç—›ã€ä¸‹è…¹å 胀,治疗2dåŽå‘生尿é‡å‡å°‘ã€å…¨èº«ä¸é€‚ç‰ç—‡çŠ¶.æŸ ¥è‚¾åŠŸç¤º:è¡€å°¿ç´ æ°®(BUN)20.7mmol/L,血清肌é…(CRE)560.3μmol/L;肾è„ç—…ç†æ£€æŸ¥ç¤º:急性肾å°ç®¡åæ»ä¼´è½»åº¦ç³»è†œå¢žç”ŸåŠä¸ªåˆ«è‚¾å °çƒç¡¬åŒ–.给予åœè¯ã€ç´§æ€¥è¡€æ¶²é€æž2次åŠå¯¹ç—‡æ”¯æŒæ²»ç–—7dåŽç—Šæ„ˆ.结论 阿昔洛韦导致肾功能衰ç«æœ€å¸¸è§ç—‡çŠ¶æ˜¯çªå‘腰痛㠀æ¶å¿ƒ,ç—…ç†å¦å¤šä¸ºè‚¾å°ç®¡ç—…å˜,患者ç»è¿‡åœè¯ã€é€æžåŠå¯¹ç—‡æ”¯æŒæ²»ç–—åŽå‡èƒ½ç—Šæ„ˆ.%Objective To investigate the histological features, clinical manifestations, treatment options and prognosis of Acyclovir-induced acute renal failure. Methods The clinical, pathological and prognosis of 1 case of Acyclovir-induced acute renal failure were reviewed respectively, and the related literature was reviewed. ResultS A middle-aged man suffering from cutaneous herpes zoster was given Acyclovir by intravenous drip and per os, when he developed acute abdominal pain and general malaise. Renal examin on showed, his serum creatinine (CRE) and blood urea nitrogen (BUN) concentrations rose to 560.3 μmol/L and 20. 7 mmol/L, respectively. The pathology of kidney exhibited acute renal tubular necrosis acompanied with slight glomerular sclerosis. Renal impairment was restored after discontinuation of Acyclovir, hemodialysis and symptomatic treatment. Conclusion Acute abdominal pain and nausea are the most common symptoms of Acyclovir-induced acute renal failure. The pathology revealed acute renal tubular necrosis. Hemodialysis, symptomatic treatment and discontinuation of Acyclovir are the effective 149. Treatment of relapse in herpes simplex on labial and facial areas and of primary herpes simplex on genital areas and "area pudenda" with low-power He-Ne laser or Acyclovir administered orally Science.gov (United States) Velez-Gonzalez, Mariano; Urrea-Arbelaez, Alejandro; Nicolas, M.; Serra-Baldrich, E.; Perez, J. L.; Pavesi, M.; Camarasa, J. M.; Trelles, Mario A. 1996-01-01 Sixty patients (greater than 16 yrs old) suffering primary or relapse genital herpes simplex viruses (HSV) and relapse labial HSV were appointed for this study. Three or more relapses were experienced per year. Patients (under treatment) were divided into two groups (distribution areas), corresponding to either labial herpes or genital herpes. These groups were sub-divided into 3 groups. The total number of labial or facial HSV patients was 36 (10 in group 1, 12 in group 2, 14 in group 3) and 24 for genital, buttocks, or 'area pudenda' HSV patients (6 in group 1, 8 in group 2, 10 in group 3). The design was a randomized, double- blind study. The setting was hospital and outpatient. The patients diagnosed as having the HVS disease were sent to the dermatology department and were assigned to a group at random. Treatment was begun as follows: During the treatment signs and symptoms were assessed and after the treatment, the relapses were also assessed (biochemical and hematological tests before and after the treatment) and the diagnosis of the HSV type I and II. The statistical evaluation of the results was performed and carried out with the SPSS and BMDP program. The relapses of the herpes infection in the lips and the face were significantly reduced (p less than 0.026) in patients treated with laser He-Ne and laser He-Ne plus Acyclovir. The interim between the relapses also increased significantly (p less than 0.005) in relation with the group treated with Acyclovir. The duration of the herpetic eruptions was clearly reduced in all locations in patients treated with laser He-Ne plus Acyclovir. No differences were noted between patients treated with laser He-Ne only or Acyclovir only. Therefore it is probable that therapeutic synergism took place. In relation with this, laser He-Ne shows the same therapeutic efficacy as Acyclovir taken orally. The association of Acyclovir and laser Ne-Ne could be an alternative method for the treatment of HSV in the face. The number 150. Self-collected genital swabs compared with cervicovaginal lavage for measuring HIV-1 and HSV-2 and the effect of acyclovir on viral shedding. Science.gov (United States)

McNicholl, Janet M; Leelawiwat, Wanna; Whitehead, Sara; Hanson, Debra L; Evans-Strickfaden, Tammy; Cheng, Chen Y; Chonwattana, Wannee; Mueanpai, Famui; Kittinunvorakoon, Chonticha; Markowitz, Lauri; Dunne, Eileen F 2017-03-01 HIV-1 and HSV-2 are frequent genital co-infections in women. To determine how self-collected genital swabs compare to provider-collected cervicovaginal lavage, paired selfcollected genital swabs and cervicovaginal lavage from women co-infected with HIV-1 and HSV-2 were evaluated. Women were in an acyclovir clinical trial and their samples were tested for HIV-1 RNA (361 samples) and HSV-2 DNA (378 samples). Virus shedding, quantity and acyclovir effect were compared. HIV-1 and HSV-2 were more frequently detected in self-collected genital swabs: 74.5% of self-collected genital swabs and 63.6% of cervicovaginal lavage had detectable HIV-1 (p ≤ 0.001, Fisher's exact test) and 29.7% of self-collected genital swabs and 19.3% of cervicovaginal lavage had detectable HSV-2 (p ≤ 0.001) in the placebo month. Cervicovaginal lavage and selfcollected genital swabs virus levels were correlated (Spearman's rho, 0.68 for HIV; 0.61 for HSV-2) and self-collected genital swabs levels were generally higher. In multivariate modeling, self-collected genital swabs and cervicovaginal lavage could equally detect the virus-suppressive effect of acyclovir: for HIV-1, proportional odds ratios were 0.42 and 0.47 and for HSV-2, they were 0.10 and 0.03 for self-collected genital swabs and cervicovaginal lavage, respectively. Self-collected genital swabs should be considered for detection and measurement of HIV-1 and HSV-2 in clinical trials and other studies as they are a sensitive method to detect virus and can be collected in the home with frequent sampling. 151. Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection Directory of Open Access Journals (Sweden) Bader Marlene 2009-04-01 Full Text Available Abstract Background Herpes simplex virus infection (HSV is a common and ubiquitous infection of the skin which causes mucocutaneous lesions called cold sores (herpes labialis or fever blisters. It is estimated that approximately 80% of the population worldwide are carriers of the Herpes simplex virus, approximately 40% suffer from recurrent recurrent infections. This study evaluates the in vitro skin permeation and penetration of penciclovir and acyclovir from commercialized creams for the treatment of herpes labialis (cold sores, using non viable excised human abdominal skin samples, which were exposed to 5 mg/cm2 of acyclovir 5% cream or penciclovir 1% cream. Methods After 24 h of cream application, excess cream was washed off and layers of stratum corneum were removed by successive tape stripping. Amounts of active ingredients having penetrated through the skin were measured, as well as the amounts in the washed-off cream, in skin strips and creams remaining in the skin. Molecular modelling was used to evaluate physicochemical differences between the drugs. Western blot analysis enabled to determine whether the marker of basal cells keratin 5 could be detected in the various tape strips. Results Application of penciclovir 1% cream yielded higher concentration of drug in the deeper layers of the epidermis as well as a higher drug flux through the skin. Molecular modelling showed two higher hydrophobic moieties for acyclovir. Presence of the basal cell marker keratin 5 was underscored in the deeper tape strips from the skin, giving evidence that both drugs can reach their target cells. Conclusion Penciclovir 1% cream has the tendency to facilitate the diffusion of the drug through the stratum corneum into the deeper epidermis layers, in which it could reach the target basal cells at effective therapeutical concentration. The small difference in the surface properties between both molecules might also contribute to favour the passage of 152. Clinical and virologic response to episodic acyclovir for genital ulcers among HIV-1 seronegative, herpes simplex virus type 2 seropositive African women: a randomized, placebocontrolled trial. Science.gov (United States) Baeten, Jared M; Reid, Stewart E; Delany-Moretlwe, Sinead; Hughes, James P; Wang, Richard S; Wilcox, Ellen; Limbada, Mohammed; Akpomiemie, Godspower; Corey, Lawrence; Wald, Anna; Celum, Connie 2012-01-01 In a randomized trial among African women with recurrent genital herpes, episodic acyclovir therapy resulted in modestly greater likelihood of lesion healing (hazard ratio [HR] = 1.48, P = 0.098; mean, 5.1 vs. 6.0 days) and cessation of herpes simplex virus shedding (HR = 1.88, P = 0.008; mean, 3.0 vs. 5.0 days) compared with placebo, similar to results of studies in high-income countries (ClinicalTrials.gov registration NCT00808405). 153. Utilization of nanotechnology to enhance percutaneous absorption of acyclovir in the treatment of herpes simplex viral infections. Science.gov (United States) Al-Subaie, Mutlaq M; Hosny, Khaled M; El-Say, Khalid Mohamed; Ahmed, Tarek A; Aljaeid, Bader M 2015-01-01 This study aimed to formulate an optimized acyclovir (ACV) nanoemulsion hydrogel in order to provide a solution for the slow, variable, and incomplete oral drug absorption in patient suffering from herpes simplex viral infection. Solubility of ACV in different oils, surfactants, and cosurfactants was explored utilizing a cubic model mixture design to obtain a nanoemulsion with minimum globule size. Preparation of an optimized ACV nanoemulsion hydrogel using a three-factor, three-level Box-Behnken statistical design was conducted. The molecular weight of chitosan (X1), percentage of chitosan (X2), and percentage of Eugenol as a skin permeation enhancer (X3) were selected to study their effects on hydrogel spreadability (Y1) and percent ACV permeated through rat skin after 2.5 hours (Y2). A pharmacokinetic study of the optimized ACV nanoemulsion hydrogel was conducted in rats. Mixtures of clove oil and castor oil (3:1 ratio), Tween 80 and Span 80 (3:1 ratio), and propylene glycol and Myo-6V (3:1 ratio) were selected as the oil, surfactant, and cosurfactant phases, respectively. Statistical analysis indicated that the molecular weight of chitosan has a significant antagonistic effect on spreadability, but has no significant effect on the percent ACV permeated. The percentage of chitosan also has a significant antagonistic effect on the spreadability and percent ACV permeated. On the other hand, the percentage of Eugenol has a significant synergistic effect on percent ACV permeated, with no effect on spreadability. The ex vivo study demonstrated that the optimized ACV nanoemulsion hydrogel showed a twofold and 1.5-fold higher permeation percentage than the control gel and marketed cream, respectively. The relative bioavailability of the optimized ACV nanoemulsion hydrogel improved to 535.2% and 244.6% with respect to the raw ACV hydrogel and marketed cream, respectively, confirming improvement of the relative bioavailability of ACV in the formulated nanoemulsion 154. Pharmacokinetics of amino acid ester prodrugs of acyclovir after oral administration: interaction with the transporters on Caco-2 cells. Science.gov (United States) Katragadda, Suresh; Jain, Ritesh; Kwatra, Deep; Hariharan, Sudharshan; Mitra, Ashim K 2008-10-01 In vivo systemic absorption of the amino acid prodrugs of acyclovir (ACV) after oral administration was evaluated in rats. Stability of the prodrugs, L-alanine-ACV (AACV), Lserine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) was evaluated in various tissues. Interaction of these prodrugs with the transporters on Caco-2 cells was studied. In vivo systemic bioavailability of these prodrugs upon oral administration was evaluated in jugular vein cannulated rats. The amino acid ester prodrugs showed affinity towards various amino acid transporters as well as the peptide transporter on the Caco-2 cells. In terms of stability, EACV was most enzymatically stable compared to other prodrugs especially in liver homogenate. In oral absorption studies, ACV and AACV showed high terminal elimination rate constants (lambda(z)). SACV and VACV exhibited approximately five-fold increase in area under the curve (AUC) values relative to ACV (pACV. C(last(T)) (concentration at the last time point) of SACV was observed to be 0.18+/-0.06 microM in plasma which is two times better than VACV and three times better than ACV. Amino acid ester prodrugs of ACV were absorbed at varying amounts (C(max)) and eliminated at varying rates (lambda(z)) thereby leading to varying extents (AUC). The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections. 155. Safety and tolerability of combination acyclovir 5% and hydrocortisone 1% cream in adolescents with recurrent herpes simplex labialis. Science.gov (United States) Strand, Anders; Böttiger, Disa; Gever, Larry N; Wheeler, William 2012-01-01 A Phase 3, open-label, multicenter study was conducted to assess the safety of the combination of 5% acyclovir and 1% hydrocortisone cream (AHC cream) in the treatment of recurrent herpes simplex labialis (HSL) in immunocompetent adolescents. Eligible subjects were aged 12 to 17 years and had a history of recurrent labial herpes with two or more episodes during the last 12 months. Subjects initiated treatment at the first signs or symptoms of a herpes recurrence-at the earliest prodromal phase and preferably before the presence of papules or vesicles. Subjects applied the cream topically five times per day for 5 days. Adverse events, categorization of recurrence (ulcerative or nonulcerative), and maximum lesion area (maximum area of an ulcerative lesion) were assessed. Of the 134 subjects analyzed for safety, 131 had data for categorization of recurrence at the post-treatment visit 3  ± 1 weeks after the last dose. Seventy-eight subjects (59.5%) had nonulcerative recurrences, and 53 (40.5%) had ulcerative recurrences. All 131 subjects reached the stage of normal skin, with no signs or symptoms, at the follow-up visit. The mean maximum lesion area in the 53 subjects with ulcerative herpes lesion was 39 mm(2). Five subjects reported five adverse events (secondary herpes labialis recurrences, n = 2; infectious rhinitis, n = 1; application site inflammation, n = 1; bronchial asthma, n = 1). All adverse events were of mild to moderate intensity. The results of this study demonstrate that the combination of AHC cream is well tolerated in the treatment of recurrent HSL in adolescents. 156. Low-dose acyclovir prophylaxis for the prevention of herpes simplex virus disease after allogeneic hematopoietic stem cell transplantation. Science.gov (United States) Kawamura, K; Wada, H; Yamasaki, R; Ishihara, Y; Sakamoto, K; Ashizawa, M; Sato, M; Machishima, T; Terasako, K; Kimura, S I; Kikuchi, M; Nakasone, H; Yamazaki, R; Kanda, J; Kako, S; Tanihara, A; Nishida, J; Kanda, Y 2013-10-01 Currently, acyclovir (ACV) at 1000 mg/day is widely used as prophylaxis in the early phase of hematopoietic stem cell transplant (HSCT) in Japan. However, low-dose ACV (200 mg/day) has been shown to prevent varicella zoster virus reactivation in the middle and late phases of HSCT. Therefore, in this study, we decreased the dose of ACV to 200 mg/day in the early phase after HSCT. We analyzed 93 consecutive herpes simplex virus (HSV)-seropositive patients who underwent allogeneic HSCT for the first time in our center between June 2007 and December 2011. Before August 2009, 38 patients received oral ACV at 1000 mg/day (ACV1000) until day 35 after HSCT, whereas 55 patients received oral ACV at 200 mg/day (ACV200) after September 2009. We compared the cumulative incidence of HSV infection in the 2 groups. Oral ACV was changed to intravenous administration because of intolerance in 66% and 45% of the patients in the ACV1000 and ACV200 groups, respectively (P = 0.060). The probability of severe stomatitis (Bearman grade II-III) was 76% and 60% in the ACV1000 and ACV200 groups, respectively (P = 0.12). The number of patients who developed HSV disease before day 100 after HSCT was 0 in the ACV1000 group and 2 in the ACV200 group, with a cumulative incidence of 3.6% (P = 0.43). HSV disease in the latter 2 patients was limited to the lips and tongue and was successfully treated with ACV or valacyclovir at a treatment dose. ACV at 200 mg/day appeared to be effective for preventing HSV disease in the early phase after HSCT. © 2013 John Wiley & Sons A/S. 157. Acyclovir-resistant herpes simplex virus type 1 in intra-ocular fluid samples of herpetic uveitis patients. Science.gov (United States) van Velzen, Monique; Missotten, Tom; van Loenen, Freek B; Meesters, Roland J W; Luider, Theo M; Baarsma, G Seerp; Osterhaus, Albert D M E; Verjans, Georges M G M 2013-07-01 Acyclovir (ACV) is the antiviral drug of choice to treat patients with herpes simplex virus type 1 (HSV-1) uveitis. The prevalence of intra-ocular ACV-resistant (ACV(R)) HSV-1 in herpetic uveitis is unknown and may have clinical consequences. In addition to its predictive value on ACV susceptibility, the polymorphic HSV-1 thymidine kinase (TK) gene facilitates differentiation between HSV-1 strains. The objective of this study was to determine the genetic composition and ACV susceptibility of the causative virus in intra-ocular fluid samples (IOF) of HSV-1 uveitis patients. The intra-ocular HSV-1 pool from 11 HSV-1 uveitis patients was determined by sequencing IOF-derived viral TK genes. The ACV susceptibility profile of the cloned intra-ocular TK variants was defined by mass spectrometry. In addition, the ganciclovir (GCV) susceptibility of the ACV(R) HSV-1 TK variants was defined. Intra-ocular fluid samples of HSV-1 uveitis patients contain HSV-1 quasispecies, principally consisting of one major and multiple genetically related minor patientspecific TK variants. Four of 10 patients analyzed had an intra-ocular ACV(R) HSV-1 of which 3 were cross-resistant to GCV. The ACV(R) profile of intra-ocular HSV-1 did not correlate with symptomatic ACV treatment. Affected eyes of HSV-1 uveitis patients are commonly infected with a patient-specific HSV-1 quasispecies, including one major and multiple genetically related minor variants. A relatively high prevalence of intra-ocular ACV(R) HSV-1, mainly ACV/GCV cross-resistant viruses, was detected in HSV-1 uveitis patients. Copyright © 2013 Elsevier B.V. All rights reserved. 158. The use of local concentrated heat versus topical acyclovir for a herpes labialis outbreak: results of a pilot study under real life conditions Directory of Open Access Journals (Sweden) Wohlrab J 2013-11-01 Full Text Available Johannes Wohlrab,1 Franziska Voß,2 Christian Müller,2 Lars C Brenn21Department of Dermatology and Venereology, Martin Luther University of HalleWittenberg, Halle, 2Department of Medical Science and Operations, Riemser Pharma GmbH, Greifswald, GermanyBackground: Frequent outbreak of herpes labialis can affect quality of life by prodromes like burning, itching, and swelling. Topical applied preparations aim to shorten the duration of symptoms, inhibit the virus replication and/or accelerate the healing process. Local concentrated heat (LCH can reduce burning, itching, or swelling of the skin by influence of mechano-heat sensitive afferent neurons.Patients and methods: To examine the effectiveness of two different topical applications (LCH versus topical acyclovir [TACV] under real life conditions, we conducted a prospective, observational, reference-controlled cohort pilot study with 103 patients. Occurrence of prodromal burning, itching, swelling, and quality of life were assessed.Results: The LCH observation group (OG showed a significantly faster improvement in all symptoms after 1-day of application than the TACV OG. The burden and duration of disease was lower and shorter in the LCH OG than in the TACV OG.Conclusions: The prodromal symptoms in recurrent herpes labialis were attenuated more effectively by LCH than by TACV.Keywords: herpes labialis, local concentrated heat, acyclovir 159. Synthesis and biological evaluation of nucleoside analogues than contain silatrane on the basis of the structure of acyclovir (ACV) as novel inhibitors of hepatitis B virus (HBV). Science.gov (United States) Han, Anyue; Li, Lingna; Qing, Kuiyou; Qi, Xiaolu; Hou, Leping; Luo, Xintong; Shi, Shaohua; Ye, Faqing 2013-03-01 Hepatitis B virus (HBV) infection causes major public health problems worldwide. Acyclovir (ACV) is mainly used to inhibit herpes simplex virus (HSV) rather than HBV. In this study, we used the combination principle to design and synthesize nucleoside analogues that contain silatrane on the basis of the structure of ACV. We found that the compounds were effective inhibitors of HBV, both in vitro and in vivo. All of the compounds showed suppressive activity on the expression of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the HepG2.2.15 cell line with low cytotoxicity. One of compounds was studied in HBV transgenic mice model, and the test results showed its ability to reduce the levels of HBsAg, HBeAg and HBV DNA by ELASE and qPCR. Furthermore, significant improvement of T lymphocyte was observed after treatment, as evaluated by flow cytometry (FCM). 160. Modification of glassy carbon electrode with a bilayer of multiwalled carbon nanotube/tiron-doped polypyrrole: Application to sensitive voltammetric determination of acyclovir Energy Technology Data Exchange (ETDEWEB) Shahrokhian, Saeed, E-mail: [email protected] [Department of Chemistry, Sharif University of Technology, Tehran 11155-3516 (Iran, Islamic Republic of); Institute for Nanoscience and Technology, Sharif University of Technology, Tehran (Iran, Islamic Republic of); Azimzadeh, Mahnaz [Department of Chemistry, Sharif University of Technology, Tehran 11155-3516 (Iran, Islamic Republic of); Amini, Mohammad K. [Department of Chemistry, Isfahan University, Isfahan (Iran, Islamic Republic of) 2015-08-01 A novel voltammetric sensor based on glassy carbon electrode (GCE) modified with a thin film of multi-walled carbon nanotubes (MWCNTs) coated with an electropolymerized layer of tiron-doped polypyrrole was developed and the resulting electrode was applied for the determination of acyclovir (ACV). The surface morphology and property of the modified electrode were characterized by field emission scanning electron microscopy and electrochemical impedance spectroscopy techniques. The electrochemical performance of the modified electrode was investigated by means of linear sweep voltammetry (LSV). The effect of several experimental variables, such as pH of the supporting electrolyte, drop size of the cast MWCNTssuspension, number of electropolymerization cycles and accumulation time was optimized by monitoring the LSV response of the modified electrode toward ACV. The best response was observed at pH 7.0 after accumulation at open circuit for 160 s. Under the optimized conditions, a significant electrochemical improvement was observed toward the electrooxidation of ACV on the modified electrode surface relative to the bare GCE, resulting in a wide linear dynamic range (0.03–10.0 μM) and a low detection limit (10.0 nM) for ACV. Besides high sensitivity, the sensor represented high stability and good reproducibility for ACV analysis, and provided satisfactory results for the determination of this compound in pharmaceutical and clinical preparations. - Highlights: • A simple method was employed to construct a thin film modified electrode. • Tirondoped polypyrrole was electropolymerized on MWCNT precast glassy carbon electrode. • Electrode surface characterization was performed by microscopic and spectroscopic techniques. • The modified electrode showed nano-molar detection limit for acyclovir. • The modified electrode was applied for the detection of ACV in pharmaceutical and clinical preparations. « 6 7 8 9 10 » « 7 8 9 10 11 » 161. QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance. Science.gov (United States) Singh, Bhupinder; Kaur, Anterpreet; Dhiman, Shashi; Garg, Babita; Khurana, Rajneet Kaur; Beg, Sarwar 2016-04-01 The current studies entail systematic quality by design (QbD)-based development of stimuli-responsive gastroretentive drug delivery systems (GRDDS) of acyclovir using polysaccharide blends for attaining controlled drug release profile and improved patient compliance. The patient-centric quality target product profile was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through Ishikawa fish bone diagram and failure mode, effect, and criticality analysis, helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. A face-centered cubic design was employed for systematic development and optimization of the concentration of sodium alginate (X 1) and gellan (X 2) as the critical material attributes (CMAs) in the stimuli-responsive formulations, which were evaluated for CQAs viz. viscosity, gel strength, onset of floatation, and drug release characteristics. Mathematical modeling was carried out for generation of design space, and optimum formulation was embarked upon, exhibiting formulation characteristics marked by excellent floatation and bioadhesion characteristics along with promising drug release control up to 24 h. Drugexcipient compatibility studies through FTIR and DSC revealed absence of any interaction(s) among the formulation excipients. In vivo pharmacokinetic studies in Wistar rats corroborated extension in the drug absorption profile from the optimized stimuli-responsive GR formulations vis-à -vis the marketed suspension (ZOVIRAX®). Establishment of in vitro/in vivo correlation (IVIVC) revealed a high degree of correlation between the in vitro and in vivo data. In a nutshell, the present investigations report the successful development of stimuli-responsive GRDDS of acyclovir, which can be applicable as a platform approach for other drugs too. 162. 阿昔洛韦ã€å¹²æ‰°ç´ æ²»ç–—ä¼ æŸ“æ€§å•æ ¸ç»†èƒžå¢žå¤šç—‡ç–—效对比%Comparing the efficacy of acyclovir and interferon on treating infectious mononucleosis Institute of Scientific and Technical Information of China (English) 黄冬梅 2012-01-01 　　ObjectiveTo compare the efficacy and satety of acyclovir and α-interferon on treating infectious mononucleosis(IM).Methods46 children with infectious mononucleosis were randomly divided into two groups and treated with acyclovir and α-interferon respectively.The efficacy and multipce clinical indicators of two groups were observed.ResultsThe excelence rate of acyclovir group and α-interferon group were respectively 86.96% and 82.61%,The two groups were no signifiant difference(p>0.05).ConclusionThe efficacy of acyclovir andα-interferon for the treatment of infectious mononuclrosis are without difference.%　　目的比较阿昔洛韦ã€Î±-å¹²æ‰°ç´ æ²»ç–—ä¼ æŸ“æ €§å•æ ¸ç»†èƒžå¢žå¤šç—‡çš„疗效åŠå®‰å…¨æ€§.方法将46ä¾‹ä¼ æŸ“æ€§å•æ ¸ç»†èƒžå¢žå¤šç—‡æ‚£å„¿éšæœºåˆ†æˆä¸¤ç»„，分别给予阿昔洛韦åŠÎ±-å¹²æ‰ °ç´ 治疗.观察两组患儿治疗疗效åŠå¤šä¸ªä¸´åºŠæŒ‡æ ‡çš„差异.结果阿昔洛韦组与α-å¹²æ‰°ç´ ç»„æœ ‰æ•ˆçŽ‡åˆ†åˆ«ä¸º86.96%å’Œ82.61%，阿昔洛韦组与α-å¹²æ‰°ç´ ç»„æ¯”è¾ƒæ— æ˜¾è‘—å·®å¼‚(P>0.05).结论阿昔洛韦ã€Î±-å¹²æ‰°ç´ ç”¨äºŽæ²»ç–— ä¼ æŸ“æ€§å•æ ¸ç»†èƒžå¢žå¤šç—‡ä¸´åºŠç–—æ•ˆæ— å·®å¼‚. 163. Hybrid molecularly imprinted polymers synthesized with 3-aminopropyltriethoxysilane-methacrylic acid monomer for miniaturized solid-phase extraction: A new and economical sample preparation strategy for determination of acyclovir in urine. Science.gov (United States) Yan, Hongyuan; Wang, Mingyu; Han, Yehong; Qiao, Fengxia; Row, Kyung Ho 2014-06-13 The miniaturized molecularly imprinted solid-phase extraction (mini-MISPE) coupled with high-performance liquid chromatography was proposed for the determination of acyclovir in urine. 1.5-mL tapered plastic centrifuge tube filled with hybrid molecularly imprinted polymers (HMIPs) was used as the cartridge of mini-MISPE, and the HMIPs synthesized with 3-aminopropyltriethoxy silane-methacrylic acid as monomer exhibited good recognition and selectivity for acyclovir. Under the optimized condition, good linear calibration was obtained in a range of 0.5-15μgmL(-1) with the correlation coefficient of 0.9994, and the recoveries at three spiked levels were 91.6-103.3% in urine with the relative standard deviation (RSD) of ≤3.5%. Excellent intra-day and inter-day repeatability were achieved with RSD of ≤2.6% and 4.0% in three different concentrations. This method combined the advantages of HMIPs and mini-MISPE, and it could become an alternative tool for analyzing the residues of acyclovir in complex urine matrices. 164. Genotypic and phenotypic characterization of the thymidine kinase of ACV-resistant HSV-1 derived from an acyclovir-sensitive herpes simplex virus type 1 strain. Science.gov (United States) Saijo, Masayuki; Suzutani, Tatsuo; De Clercq, Erik; Niikura, Masahiro; Maeda, Akihiko; Morikawa, Shigeru; Kurane, Ichiro 2002-12-01 Twenty-four strains of acyclovir (ACV)-resistant (ACV(r)) herpes simplex virus type 1 (HSV-1) were generated from the HSV-1 TAS strain by exposure to ACV, and the genotype and phenotype of the thymidine kinase (TK) from these mutants were analyzed. The TK polypeptide of the ACV(r) HSV-1 strains was examined by Western blot using an antiHSV-1 TK rabbit serum. The sensitivity of each strain to ACV, foscarnet and cidofovir (CDV) was also determined. A single guanine (G) insertion or a single cytosine (C) deletion was detected in 12 of the 24 ACV(r) strains at the G or C homopolymer stretches within the TK gene. Genotypic analysis predicted that two thirds of the ACV(r) HSV-1 strains expressed truncated TK polypeptides, while one third expressed viral TK polypeptide with a single amino acid substitution at various sites. Western blot abnormalities in the viral TK polypeptides were identified in 21 ACV(r) strains. There was an inverse correlation between the susceptibility of the HSV-1 mutant strains to ACV and that to CDV. Nucleotide sequencing of the TK gene and Western blot analysis of the viral TK polypeptides are considered to be one of the methods for predicting virus sensitivity to ACV and CDV. 165. Characterization of DNA polymerase-associated acyclovir-resistant herpes simplex virus type 1: mutations, sensitivity to antiviral compounds, neurovirulence, and in-vivo sensitivity to treatment. Science.gov (United States) Wang, Li-Xin; Takayama-Ito, Mutsuyo; Kinoshita-Yamaguchi, Hitomi; Kakiuchi, Satsuki; Suzutani, Tatsuo; Nakamichi, Kazuo; Lim, Chang-Kweng; Kurane, Ichiro; Saijo, Masayuki 2013-01-01 Acyclovir (ACV)-resistant (ACV(r)) mutants were generated from plaque-purified ACV-sensitive herpes simplex virus type 1 (HSV-1) by culturing the virus in Vero cells in the presence of 2-amino-7-(1,3-dihydroxy-2-propoxymethyl) purine (S2242). Three DNA polymerase (DNApol)-associated ACV(r) HSV-1 generated under ACV selection in a previous study (Suzutani, T., Ishioka, K., De Clercq, E., et al., Antimicrob. Agents Chemother., 47, 1707-1713, 2003) were also included. The sensitivity of the mutants to other antivirals and their neurovirulence were determined. The treatment efficacy of ACV and ganciclovir (GCV) against ACV(r) HSV-1 infections was evaluated in mice. Amino acid substitutions were demonstrated in conserved regions II and III in DNApol in 5 of the 6 mutants, while the other substitution was located in non-conserved regions. DNApolassociated ACV(r) clones showed cross-resistance to foscarnet, penciclovir, and vidarabine but were sensitive or hypersensitive to GCV, brivudin, sorivudine, and spongothymidine. The ACV(r) clone with an N815S mutation in DNApol showed similar neurovirulence to that of the parent virus; however, those with other mutations showed attenuation. GCV was effective in the treatment of the ACV(r) clone with similar virulence to that of parent HSV-1, while ACV was less effective in mice. These results indicate the importance of the characterization of HSV-1 isolates for the proper treatment of HSV-1 infections exhibiting ACV-resistance. 166. Binding characteristics of homogeneous molecularly imprinted polymers for acyclovir using an (acceptor-donor-donor)-(donor-acceptor-acceptor) hydrogen-bond strategy, and analytical applications for serum samples. Science.gov (United States) Wu, Suqin; Tan, Lei; Wang, Ganquan; Peng, Guiming; Kang, Chengcheng; Tang, Youwen 2013-04-12 This paper demonstrates a novel approach to assembling homogeneous molecularly imprinted polymers (MIPs) based on mimicking multiple hydrogen bonds between nucleotide bases by preparing acyclovir (ACV) as a template and using coatings grafted on silica supports. (1)H NMR studies confirmed the AAD-DDA (A for acceptor, D for donor) hydrogen-bond array between template and functional monomer, while the resultant monodisperse molecularly imprinted microspheres (MIMs) were evaluated using a binding experiment, high performance liquid chromatography (HPLC), and solid phase extraction. The Langmuir isothermal model and the Langmuir-Freundlich isothermal model suggest that ACV-MIMs have more homogeneous binding sites than MIPs prepared through normal imprinting. In contrast to previous MIP-HPLC columns, there were no apparent tailings

for the ACV peaks, and ACV-MIMs had excellent specific binding properties with a Ka peak of 3.44 × 10(5)M(-1). A complete baseline separation is obtained for ACV and structurally similar compounds. This work also successfully used MIMs as a specific sorbent for capturing ACV from serum samples. The detection limit and mean recovery of ACV was 1.8 ng/mL(-1) and 95.6%, respectively, for molecularly imprinted solid phase extraction coupled with HPLC. To our knowledge, this was the first example of MIPs using AADDDA hydrogen bonds. 167. Modification of glassy carbon electrode with a bilayer of multiwalled carbon nanotube/tiron-doped polypyrrole: Application to sensitive voltammetric determination of acyclovir. Science.gov (United States) Shahrokhian, Saeed; Azimzadeh, Mahnaz; Amini, Mohammad K 2015-08-01 A novel voltammetric sensor based on glassy carbon electrode (GCE) modified with a thin film of multi-walled carbon nanotubes (MWCNTs) coated with an electropolymerized layer of tiron-doped polypyrrole was developed and the resulting electrode was applied for the determination of acyclovir (ACV). The surface morphology and property of the modified electrode were characterized by field emission scanning electron microscopy and electrochemical impedance spectroscopy techniques. The electrochemical performance of the modified electrode was investigated by means of linear sweep voltammetry (LSV). The effect of several experimental variables, such as pH of the supporting electrolyte, drop size of the cast MWCNTssuspension, number of electropolymerization cycles and accumulation time was optimized by monitoring the LSV response of the modified electrode toward ACV. The best response was observed at pH7.0 after accumulation at open circuit for 160 s. Under the optimized conditions, a significant electrochemical improvement was observed toward the electrooxidation of ACV on the modified electrode surface relative to the bare GCE, resulting in a wide linear dynamic range (0.03-10.0μ M) and a low detection limit (10.0 nM) for ACV. Besides high sensitivity, the sensor represented high stability and good reproducibility for ACV analysis, and provided satisfactory results for the determination of this compound in pharmaceutical and clinical preparations. Copyright © 2015 Elsevier B.V. All rights reserved. 168. Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections. Science.gov (United States) Katragadda, Suresh; Gunda, Sriram; Hariharan, Sudharshan; Mitra, Ashim K 2008-07-09 To evaluate in vivo corneal absorption of the amino acid prodrugs of acyclovir (ACV) using a topical well model and microdialysis in rabbits. Stability of L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) prodrugs was evaluated in various ocular tissues. Dosedependent toxicity of these prodrugs was also examined in rabbit primary corneal epithelial cell culture (rPCEC) using 96-well based cell proliferation assay. In vivo ocular bioavailability of these compounds was also evaluated with a combination of topical well infusion and aqueous humor microdialysis techniques. Among the amino acid ester prodrugs, SACV was most stable in aqueous humor. Enzymatic degradation of EACV was the least compared to all other prodrugs. Cellular toxicity of all the prodrugs was significantly less compared to trifluorothymidine (TFT) at 5mM. Absorption rate constants of all the compounds were found to be lower than the elimination rate constants. All the prodrugs showed similar terminal elimination rate constants (lambda(z)). SACV and VACV exhibited approximately two-fold increase in area under the curve (AUC) relative to ACV (pACV, respectively. Amino acid ester prodrugs of ACV were absorbed through the cornea at varying rates (ka) thereby leading to varying extents (AUC). The amino acid ester prodrug, SACV owing to its enhanced stability, comparable AUC and high concentration at last time point (Clast) seems to be a promising candidate for the treatment of ocular HSV infections. 169. Protocol for German trial of Acyclovir and corticosteroids in Herpes-simplex-virus-encephalitis (GACHE: a multicenter, multinational, randomized, double-blind, placebo-controlled German, Austrian and Dutch trial [ISRCTN45122933 Directory of Open Access Journals (Sweden) Schielke Eva 2008-10-01 Full Text Available Abstract Background The treatment of Herpes-simplex-virus-encephalitis (HSVE remains a major unsolved problem in Neurology. Current gold standard for therapy is acyclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains up to 15%, less than 20% of patients are able to go back to work, and the majority of patients suffer from severe disability. This is a discouraging, unsatisfactory situation for treating physicians, the disabled patients and their families, and constitutes an enormous burden to the public health services. The information obtained from experimental animal research and from recent retrospective clinical observations, indicates that a substantial benefit in outcome can be expected in patients with HSVE who are treated with adjuvant dexamethasone. But currently there is no available evidence to support the routine use of adjuvant corticosteroid treatment in HSVE. A randomized multicenter trial is the only useful instrument to address this question. Design GACHE is a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial of treatment with acyclovir and adjuvant dexamethasone, as compared with acyclovir and placebo in adults with HSVE. The statistical design will be that of a 3-stage-group sequential trial with potential sample size adaptation in the last stage. Conclusion 372 patients with proven HSVE (positive HSV-DNA-PCR, aged 18 up to 85 years; with focal neurological signs no longer than 5 days prior to admission, and who give informed consent will be recruited from Departments of Neurology of academic medical centers in Germany, Austria and The Netherlands. Sample size will potentially be extended after the second interim analysis up to a maximum of 450 patients. Trial Registration Current Controlled Trials ISRCTN45122933 170. Analysis of the combined effect of local UV and acyclovir on herpes zoster%局部紫外线è”åˆé˜¿æ˜”洛韦治疗带状疱疹的疗效观察 Institute of Scientific and Technical Information of China (English) æŽæ™ºå¿ 2010-01-01 目的 观察局部紫外线照射è”åˆé˜¿æ˜”洛韦治疗带状疱疹的临床疗效.方法 138例带状疱疹患者分为2组.æ²»ç–—ç»„ç”¨é˜¿æ˜”æ´›éŸ¦å £æœæ²»ç–—åŠ å±€éƒ¨ç´«å¤–çº¿ç…§å°„;对照组å•ç”¨é˜¿æ˜”洛韦治疗带状疱疹.结果 治疗组有效率(97.92%)æ˜Žæ˜¾é«˜äºŽå¯¹ç… §ç»„(P＜0.05),带状疱疹åŽé—神ç»ç—›å‘生率亦比对照组明显é™ä½Ž.结论 局部紫外线è”åˆé˜¿æ˜”洛韦治疗带状疱疹起效快,疗程çŸ,ç– —效显著,且能防æ¢åŽç¥žç»ç—›çš„å‘生.%Objective To understand partial response of herpes zoster to ultraviolet radiation,and find other methods of herpes zoster treatment.Methods 138 cases of herpes zoster were divided into two groups.The treatment group received oral acyclovir and local ultraviolet irradiation while the control group received acyclovir alone.Results Treatment efficacy was significantly higher in the treatment group(97.92%)compared to the control( P ＜ 0.05),and the incidence of postherpetic neuralgia was also significantly lower in the treatment group.Conclusion Local UV combined with acyclovir treatment of herpes zoster produces fast,brief duration,significant effects,and can prevent the occurrence of postherpetic neuralgia. 171. ä¸è¯ä½æ²»è€å¹´HIV/AIDSåˆå¹¶å¸¦çŠ¶ç–±ç–¹ç–—效观察%Effect of traditional Chinese medicine combined with acyclovir on herpes zoster in elderly with HIV/AIDS Institute of Scientific and Technical Information of China (English) æ¢é£žç«‹; è‹æ–‡æ¡‚; 何艳英; 余丰; æ–¹é¹ 2012-01-01 Objective It is to observe the effect of traditional Chinese medicine combined with acyclovir on herpes zoster in 30 elderly patients with HIV/AIDS. Methods Sixty elderly patients with HIV/AIDS were randomly divided into two groups. Thirty patients in treatment group were treated with external application of traditional Chinese medicine combined with acyclovir; thirty patients in control group were treated with acyclovir only. Results In treatment group, 17 cases were cured and 9 cases were improved, the effective rate was 87% . In control group, 14 cases were cured and 4 cases were improved, the effective rate was 60% . There was significantly difference in effective rate between both groups. The cured time of skin lesions was ( 16.17 ± 5. 47 ) days in treatment group, and was ( 20. 50 ± 6. 35 ) days in control group, there was significant difference between both groups. Conclusion External application of traditional Chinese medicine combined with acyclovir can shorten healing time of skin lesions caused by herpes zoster in the elderly with IV/AIDS and increase cure rate.%目的 探讨ä¸è¯å¤–æ•·é…åˆé˜¿æ˜”洛韦治疗è€å¹´HIV/AIDSåˆå¹¶å¸¦çŠ¶ç–±ç–¹çš„疗效.方法 60例患者 éšæœºåˆ†ä¸º2组,治疗组30例用ä¸è¯å¤–æ•·åŠé˜¿æ˜”洛韦é™è„‰æ»´æ³¨,对照组30例å•ç”¨é˜¿æ˜”洛韦é™è„‰æ»´æ³¨.结果 治疗组治愈17 例,å ¥½è½¬9例,未愈4例,治愈好转率87%(26/30);对照组治愈14 例,好转4例,未愈12例,治愈好转率60%(18/30);2ç»„æ²»æ„ˆå ¥½è½¬çŽ‡æ¯”较有显著性差异(î…ž2 =5.455,P20 x 10(9)/l were 9 and 11 days. Severe neutropenia (