ABSTRACT

The importance of metabolism during percutaneous absorption depends on the structure and biological activity of the penetrating compounds and metabolites. For benzo[a]pyrene, metabolism in the skin is necessary for its activation to a proximate skin carcinogen. The extent of cutaneous metabolism in vivo is difficult to differentiate from systemic metabolism. Few studies have evaluated animal models for human skin metabolism. Skin should be freshly obtained from human or animal sources. Human skin from surgical procedures seems most suitable for metabolism studies. Flow-through diffusion cells are preferable for maintaining the viability of skin because the receptor fluid is continuously replenished. Tissue culture media, such as minimal essential media, can be used to maintain skin viability in a flow-through diffusion cell. Skin metabolism is frequently expressed in terms of percent of absorbed dose metabolized. Significant metabolism of topically applied compounds can occur during percutaneous absorption in human and animal skin.