Pharmacokinetic models of dermal absorption

Many studies have used pharmacokinetic (compartment) models for skin to predict or analyze dermal absorption of chemicals. Comparing these models is difficult because the relationships between rate constants and the physicochemical parameters were not always defined clearly, simplifying assumptions built into models sometimes were not stated, and which skin layers were included often were not specified. In this paper we review and compare published one- and two-compartment models for which rate constants were expressed in terms of the physicochemical and physical properties of the skin (i.e., diffusion coefficients, partition coefficients and thickness). Nine one-compartment and two two-compartment models are presented with a consistent nomenclature and clearly defined assumptions. In addition, methods used for estimating the physicochemical parameters required by the various models are summarized. These eleven compartment models are compared with calculations from a two-membrane skin model that corresponds better with skin function. Many of the compartment models do not predict key characteristics of the two-membrane skin model, especially the effect of blood flow on skin concentration and penetration rates, even when the same input parameters were used. The compartment models developed by Kubota and by McCarley are better predictors of the two-membrane model results, because these models were developed to match characteristics of the membrane model. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.