Lipophilicity and its relationship with passive drug permeation.
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.
Department of Pharmaceutical Technology, Friedrich-Schiller-Universität Jena, Lessingstrasse 8, 07743 Jena, Germany. Xiangli.Liu@uni-jena.de
Xiangli
X
Liu
Bernard
B
Testa
Alfred
A
Fahr
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D010539:Permeability; D010599:Pharmacokinetics; D012867:Skin / Q000378:metabolism
D008563:Membrane Lipids