Perspectives in Drug Discovery and Design

, Volume 19, Issue 1, pp 179–211 | Cite as

The influence of lipophilicity on the pharmacokinetic behavior of drugs: Concepts and examples

  • Bernard Testa
  • Patrizia Crivori
  • Marianne Reist
  • Pierre-Alain Carrupt
Article

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 

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Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Bernard Testa
    • 1
  • Patrizia Crivori
    • 1
  • Marianne Reist
    • 1
  • Pierre-Alain Carrupt
    • 1
  1. 1.Institut de Chimie Thérapeutique, BEPUniversité de LausanneLausanneSwitzerland

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