The influence of lipophilicity on the pharmacokinetic behavior of drugs [PDF]

The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples Perspectives in Drug Discovery and Design September 2000, Volume 19, Issue 1, pp 179–211 | Cite as Bernard Testa (1) Patrizia Crivori (1) Marianne Reist (1) Pierre-Alain Carrupt (1) 1. Institut de Chimie Thérapeutique, BEP, Université de Lausanne, Lausanne, Switzerland Article 1.3k Downloads 97 Citations

Abstract In this review, we first examine the contextual background of structure–pharmacokinetic relationships. Some concepts in drug disposition are briefly recalled, and inherent difficulties instructure–pharmacokinetic relationships are outlined. Lipophilicity is then investigated in the light of the intermolecular and intramolecular interactions it encodes. In the main body of the review, a number of pharmacokinetic processes are examined for their relations with lipophilicity. These processes are taken in a logical sequence of permeation, absorption (intestine, skin, cornea, brain), plasma protein binding, tissue distribution, volume of distribution and renal clearance. Relations between metabolism and lipophilicity are more complex, since biotransformation involves both low-energy (enzyme binding) and high-energy (catalysis) processes. Only the former may be related to lipophilicity. The conclusion argues against faulty statistics and over-interpretation. adipose tissue storage blood–brain barrier permeation gastrointestinal absorption lipophilicity metabolism permeation plasma protein binding renal clearance This revised version was published online in August 2006 with corrections to the Cover Date. This is a preview of subscription content, log in to check access

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About this article Cite this article as: Testa, B., Crivori, P., Reist, M. et al. Perspectives in Drug Discovery and Design (2000) 19: 179. https://doi.org/10.1023/A:1008741731244 DOI (Digital Object Identifier) https://doi.org/10.1023/A:1008741731244 Publisher Name Kluwer Academic Publishers Print ISSN 0928-2866 Online ISSN 1573-9023 About this journal Reprints and Permissions

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