Skin penetration and metabolism of topically applied chemicals in six XXXX species, including @entity1 : an in vitro study with @entity3014 and @entity251 .

@entity1 @entity251 @entity19 @entity840 @entity95 @entity3014 @entity35 @entity3984
Percutaneous absorption of chemicals is generally considered a diffusional process, with the rate-limiting barrier being the nonviable stratum corneum. Because viable skin possesses enzyme activities, including those involved in the metabolism of xenobiotics, the extent to which cutaneous metabolism may influence the percutaneous fate of topically applied chemicals in the skin was examined in @entity1 skin maintained as short-term organ cultures. Skin samples from @entity19 , @entity35 , @entity95 , @entity840 , marmoset, and @entity1 were examined. The results from studies with @entity3014 (BP) and @entity251 showed that, in all species, metabolic viability was a major factor involved in the in vitro skin permeation of surface-applied chemicals. Permeation was accompanied by extensive cutaneous "first pass" metabolism; both parent compounds and a full spectrum of metabolites were found in the receptor fluid from viable skin preparations. However, in previously frozen nonviable skin preparations, essentially only unchanged parent compounds were detected in the receptor fluid. Permeation of BP and @entity251 was highest in @entity19 skin, and significant species variations in the metabolite profiles were observed. Studies with @entity19 skin also demonstrated that induction of cutaneous drug-metabolizing enzymes can result in a two- to threefold increase in the in vitro permeation of topical BP, and a significant reduction in permeation was observed when @entity3984 was added to the perfusion medium. These results indicate that diffusional and metabolic processes are intimately involved in the percutaneous fate of surface-applied chemicals. The relative importance of these processes is dependent upon the physicochemical properties of the compounds and the metabolic capabilities of the skin toward the compounds in question. Furthermore, these findings suggest that meaningful in vitro studies on skin absorption should consider both diffusion and cutaneous biotransformation of the applied compound.
