[Stereoselectivity of skin carboxylesterase metabolism].
OBJECTIVE
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.


CONCLUSIONS
Human carboxylesterase-2 is the main hydrolytic enzyme of prodrugs in percutaneous absorption, and shows metabolic stereoselectivity to prodrugs with chiral esters.
Zhu
Quan-gang
QG
Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Hu
Jin-hong
JH
Zeng
Hua-wu
HW
D000328:Adult; D043182:Carboxylesterase / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D007660:Ketoprofen / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000201:enzymology; D011355:Prodrugs / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000201:enzymology*; D013237:Stereoisomerism
D011355:Prodrugs; D012333:RNA, Messenger; D007660:Ketoprofen; D043182:Carboxylesterase