Stereoselective glucuronidation of carvedilol by Chinese liver microsomes / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
;
(12): 756-764, 2007.
Article
in English
| WPRIM
| ID: wpr-277333
ABSTRACT
<p><b>OBJECTIVE</b>To study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Propanolamines
/
Stereoisomerism
/
Microsomes, Liver
/
Carbazoles
/
China
/
Glucuronic Acid
/
Glucuronides
/
Metabolism
Country/Region as subject:
Asia
Language:
English
Journal:
Journal of Zhejiang University. Science. B
Year:
2007
Type:
Article
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