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 (v.e.) both contribute a significant resistance to chemical penetration and thus, both should be included in the model. This paper describes two-compartment models that represent the sc and the ve separately by extending the procedures previously developed for one-compartment models. The two-compartment models described here were developed by matching characteristics of a two-membrane model of skin. These compartment models were compared with membrane representations of the s.c. and v.e. for several different dermal exposure scenarios. When valid, which it is for many chemical exposure scenarios, the two-compartment model developed using characteristic times of the membrane model (model B2) more closely represents the two-membrane model than the model developed with equilibrium conditions of the membrane model (model B1). When model B2 is invalid, then model B1 is recommended. Criteria are provided for choosing from the various one- or two-compartment model options.