Drug permeation in biomembranes: in vitro and in silico prediction and influence of physicochemical properties

Eur J Pharm Sci. 2004 Sep;23(1):13-47. doi: 10.1016/j.ejps.2004.05.009.

Abstract

In the past decades, it has become increasingly apparent that in addition to therapeutic effect, drugs need to exhibit favourable absorption, distribution, metabolism and excretion (ADME) characteristics to produce a desirable response in vivo. As the recent progress in drug discovery technology enables rapid synthesis of vast numbers of potential drug candidates, robust methods are required for the effective screening of compounds synthesized within such programs, so that compounds with poor pharmacokinetic properties can be rejected at an early stage of drug development. Furthermore, a viable in silico method would save resources by enabling virtual screening of drug candidates already prior to synthesis. This review gives a general overview of the approaches aimed at predicting biological permeation, one of the cornerstones behind the ADME behaviour of drugs. The most important experimental and computational models are reviewed. Physicochemical factors underlying the permeation process are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Algorithms
  • Animals
  • Cell Membrane Permeability
  • Chemical Phenomena
  • Chemistry, Physical
  • Computer Simulation
  • Humans
  • Membranes / metabolism
  • Membranes, Artificial
  • Models, Molecular
  • Pharmaceutical Preparations / chemistry
  • Pharmaceutical Preparations / metabolism*

Substances

  • Membranes, Artificial
  • Pharmaceutical Preparations