Stereoselectivity of skin carboxylesterase metabolism

Aim To study the stereoselectivity of skin carboxylesterase metabolism and its molecular biological foundation for improving drug percutaneous absorption. Methods Ketoprofen ethyl ester was used as a model drug, and skin homogenate was applied for studying the stereoselectivity of carboxylesterase metabolism. Human liver L02 cell was used as control of carboxylesterase expression, and RT-PCR was used for studying the expression of carboxylesterase. Results The main metabolite of ketoprofen ethyl ester in human skin homogenate was R-ketoprofen. Human carboxylesterase-2 was highly expressed in skin and its cells. However, the expression of human carboxylesterase-1 was very weak or not detectable. Conclusion Human carboxylesterase-2 is the main hydrolytic enzyme of prodrugs in percutaneous absorption, and shows metabolic stereoselectivity to prodrugs with chiral esters.