Stereoselective glucuronidation of carvedilol by Chinese liver microsomes.
- Author:
Lin-ya YOU
1
;
Chun-na YU
;
Sheng-gu XIE
;
Shu-qing CHEN
;
Su ZENG
Author Information
- Publication Type:Journal Article
- MeSH: Carbazoles; metabolism; China; Glucuronic Acid; metabolism; Glucuronides; metabolism; Microsomes, Liver; metabolism; Propanolamines; metabolism; Stereoisomerism
- From: Journal of Zhejiang University. Science. B 2007;8(10):756-764
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes.
METHODSThe 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.
RESULTSTwo 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.
CONCLUSIONThese 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.
