Lipophilicity and its relationship with passive drug permeation

Pharm Res. 2011 May;28(5):962-77. doi: 10.1007/s11095-010-0303-7. Epub 2010 Oct 30.


In this review, we first summarize the structure and properties of biological membranes and the routes of passive drug transfer through physiological barriers. Lipophilicity is then introduced in terms of the intermolecular interactions it encodes. Finally, lipophilicity indices from isotropic solvent systems and from anisotropic membrane-like systems are discussed for their capacity to predict passive drug permeation across biological membranes such as the intestinal epithelium, the blood-brain barrier (BBB) or the skin. The broad evidence presented here shows that beyond the predictive power of lipophilicity parameters, the various intermolecular forces they encode allow a mechanistic interpretation of passive drug permeation.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism*
  • Humans
  • Intestinal Mucosa / metabolism
  • Membrane Lipids / chemistry*
  • Membrane Lipids / metabolism
  • Permeability
  • Pharmacokinetics*
  • Skin / metabolism


  • Membrane Lipids