Cutaneous metabolism during in vitro percutaneous absorption

The skin is a portal of entry and the largest organ of the body. It has been shown to contain the major enzymes found in other tissues of the body (1). Topically applied compounds may be metabolized in skin resulting in altered pharmacologic or toxicologic activity. The metabolism of benzo[a]pyrene applied to mouse skin floating in an organ culture demonstrated the potential importance of metabolism of chemicals during percutaneous absorption (2). A flow-through diffusion cell was subsequently developed to aid in quantitating skin absorption and metabolism (3). Viability of skin in the diffusion cell, which was assessed by light microscopy, was found to be maintained for at least 17 h (3). The viability of pig skin was maintained in flow-through cells by using tissue culture media; skin-mediated hydrolysis of diethyl malonate was observed (4). The suitability of these conditions to maintain skin viability was assessed in initial studies by the ability to graft the skin to nude mice (5).