Physiologically relevant two-compartment pharmacokinetic models for skin

Pharmacokinetic (compartment) models for skin have been used to predict or analyze absorption of chemical into and through skin. For highly lipophilic chemicals. the stratum corneum (sc) and the viable epidermis (ve) both con tribute a significant resistance to chemical penetration and thus, both sho uld be included in the model. This paper describes two-compartment models t hat represent the sc and the ve separately br extending the procedures prev iously developed for one-compartment models. The two-compartment models des cribed here were developed by matching characteristics of a tao-membrane mo del of skin. These compartment models were compared with membrane represent ations of the sc and ve for several different dermal exposure scenarios. Wh en valid. which it is for many chemical exposure scenarios, the two-compart ment model developed using characteristic times of the membrane model (mode l B2) more closely represents the two-membrane model than the model develop ed with equilibrium conditions of the membrane model (model B1). When model B2 is invalid, then model B1 is recommended. Criteria are provided for cho osing from the various one- or tno-compartment model options. (C) 2000 Wile y-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 12 12-1235, 2000.