| Biotechnology |
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| Stereoselective glucuronidation of carvedilol by Chinese liver microsomes |
| YOU Lin-ya, YU Chun-na, XIE Sheng-gu, CHEN Shu-qing, ZENG Su |
| Department of Drug Metabolism and Pharmaceutical Analysis, School of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China |
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Abstract 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 β-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-β-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 Km and Vmax for (S)-CARV and (R)-CARV enantiomers were (118±44) µmol/L, (2 500±833) pmol/(min·mg protein) and (24±7) µmol/L, (953±399) pmol/(min·mg protein), respectively. Conclusion: 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.
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Received: 02 March 2007
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