Physicochemical interpretation of the pharmacokinetics of percutaneous absorption.

Theoretical expressions are derived to predict the amount of a drug reaching the dermal capillaries as a function of simple physicochemical parameters. The mathematical approach involves the solution of the diffusion equation for the drug in the skin using the technique of Laplace transformation. First-order kinetics are assumed for the absorption of drug from the vehicle into the skin and for uptake into the capillaries. The relative importance of these different processes (absorption from vehicle, diffusion through the skin, and capillary removal) involved in the percutaneous penetration of a drug is discussed, and their influence upon the time course of the absorption phenomenon is illustrated.