Stereoselectivity of skin carboxylesterase metabolism.
- Author:
Quan-gang ZHU
1
;
Jin-hong HU
;
Hua-wu ZENG
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Carboxylesterase; genetics; metabolism; Cell Line; Cells, Cultured; Humans; Ketoprofen; metabolism; Liver; cytology; enzymology; Prodrugs; metabolism; RNA, Messenger; genetics; metabolism; Skin; enzymology; Stereoisomerism
- From: Acta Pharmaceutica Sinica 2005;40(4):322-326
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo study the stereoselectivity of skin carboxylesterase metabolism and its molecular biological foundation for improving drug percutaneous absorption.
METHODSKetoprofen 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.
RESULTSThe 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.
CONCLUSIONHuman carboxylesterase-2 is the main hydrolytic enzyme of prodrugs in percutaneous absorption, and shows metabolic stereoselectivity to prodrugs with chiral esters.
