Pharmacokinetic models of dermal absorption

✍ Scribed by Kelly D. Mccarley; Annette L. Bunge

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 280 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1120

✦ Synopsis

Many studies have used pharmacokinetic (compartment) models for skin to predict or analyze dermal absorption of chemicals. Comparing these models is dif-®cult because the relationships between rate constants and the physicochemical parameters were not always de®ned clearly, simplifying assumptions built into models sometimes were not stated, and which skin layers were included often were not speci®ed. 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 coef®cients, partition coef®cients and thickness). Nine one-compartment and two two-compartment models are presented with a consistent nomenclature and clearly de®ned 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 ¯ow 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.