Skin as an active metabolizing barrier I: Theoretical analysis of topical bioavailability.

A model and explicit equations were developed to be used in the experimental design and data evaluation of situations where simultaneous metabolism and transport of drugs occur in the skin. By treating the skin as a two-ply laminate composed of the stratum corneum and the viable epidermis, which contains most of the catabolic enzymes that might render a drug inactive by metabolism, equations were developed permitting the in vitro assessment of factors that may affect topical bioavailability in vivo. Two situations were investigated. In the first, the drug was placed on the dermis side of the diffusion cell and did not penerate the stratum corneum. In the second, the drug, placed on the epidermis side, penetrated the stratum corneum and then passed through the metabolizing epidermis. Expressions for determining the metabolic rate constant from experimental data along with concentration profiles and flux expressions are given both for the drug and its metabolite.