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

In this review, we first examine the contextual background of structure-pha rmacokinetic relationships. Some concepts in drug disposition are briefly r ecalled, and inherent difficulties in structure-pharmacokinetic relationshi ps are outlined. Lipophilicity is then investigated in the light of the int ermolecular and intramolecular interactions it encodes. In the main body of the review, a number of pharmacokinetic processes are examined for their r elations with lipophilicity. These processes are taken in a logical sequenc e of permeation, absorption (intestine, skin, cornea, brain), plasma protei n binding, tissue distribution, volume of distribution and renal clearance. Relations between metabolism and lipophilicity are more complex, since bio transformation involves both low-energy (enzyme binding) and high-energy (c atalysis) processes. Only the former may be related to lipophilicity. The c onclusion argues against faulty statistics and over-interpretation.