Physical model evaluation of topical prodrug delivery--simultaneous transport and bioconversion of vidarabine-5'-valerate V: Mechanistic analysis of influence of nonhomogeneous enzyme distributions in hairless mouse skin.

The mathematical problem of simultaneous transport and metabolism in the case of nonuniform enzyme distributions in the skin was solved, and the solutions were used for analyzing experimental data. Experimental data were obtained from permeation experiments with 3H-vidarabine and its 5'-valerate using cellophane tape-stripped hairless mouse skin. Results of the analyses revealed that the esterase activity was four to nine times higher in the epidermis than in the dermis, whereas the deaminase activity was about the same in the two strata. These results were in good agreement with independent experiments using tissue homogenates. The enzyme distributions and the previously reported diffusivities were employed in generating concentration profiles for the prodrug and the drug in the skin. These results may be used in predicting the possible therapeutic effect of the prodrug when it is topically applied.