| Autor: |
Stehle RG; Pharmaceutics, Upjohn Company, Kalamazoo, Michigan 49001., Ho NF, Barsuhn CL, Stefanski KJ |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of theoretical biology [J Theor Biol] 1989 May 09; Vol. 138 (1), pp. 1-15. |
| DOI: |
10.1016/s0022-5193(89)80174-2 |
| Abstrakt: |
A comprehensive biophysical model for the topical delivery of a drug and its single, locally active metabolite is proposed. This elaboration of the simpler case, in which the drug converts irreversibly to a pharmacologically active metabolite in the tissue, allows for enzymatic interconversion between drug and metabolite. Exact mathematical expressions give concentration-distance relationships of drug and metabolite as well as fluxes of the two molecules in terms of concentration of drug applied to the stratum corneum, permeability coefficient of drug in the stratum corneum, diffusion coefficients of drug and metabolite in the viable tissues (epidermis and dermis), rate constants for the two enzyme systems, and the thickness of the viable tissue. Constants included in the mathematical expressions can be evaluated independently by appropriate in vitro experiments with freshly excised animal skin. The model can then predict what physiochemical drug constants will lead to maximal levels of active metabolite at the site of activity within the skin. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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