Stereoselective glucuronidation of carvedilol by Chinese liver microsomes.
OBJECTIVE
To study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes.


METHODS
The metabolites of CARV were identified by a hydrolysis reaction with beta-glucuronidase and HPLC-MS/MS. The enzyme kinetics for CARV enantiomers glucuronidation was determined by a reversed phase-high pressure liquid chromatography (RP-HPLC) assay using (S)-propafenone as internal standard after precolumn derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylisothiocyanate.


RESULTS
Two CARV glucuronides were found in three Chinese liver microsomes incubated with CARV. The non-linear regression analysis showed that the values of K(m) and V(max) for (S)-CARV and (R)-CARV enantiomers were (118+/-44) micromol/L, (2 500+/-833) pmol/(min.mg protein) and (24+/-7) micromol/L, (953+/-399) pmol/(min.mg protein), respectively.


CONCLUSIONS
These results suggested that there was a significant (P<0.05) stereoselective glucuronidation of CARV enantiomers in three Chinese liver microsomes, which might partly explain the enantioselective pharmacokinetics of CARV.
You
Lin-ya
LY
Department of Drug Metabolism and Pharmaceutical Analysis, School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Yu
Chun-na
CN
Xie
Sheng-gu
SG
Chen
Shu-qing
SQ
Zeng
Su
S
D002227:Carbazoles / Q000378:metabolism*; D000077261:Carvedilol; D002681:China; D020723:Glucuronic Acid / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D011412:Propanolamines / Q000378:metabolism*; D013237:Stereoisomerism
D002227:Carbazoles; D020719:Glucuronides; D011412:Propanolamines; D000077261:Carvedilol; D020723:Glucuronic Acid