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Stereoselective glucuronidation of carvedilol by Chinese liver microsomes

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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 K m and V max for (S)-CARV and (R)-CARV enantiomers were (118±44) μmol/L, (2500±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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Authors and Affiliations

  1. Department of Drug Metabolism and Pharmaceutical Analysis, School of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China

    You Lin-ya, Yu Chun-na, Xie Sheng-gu, Chen Shu-qing & Zeng Su

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  1. You Lin-ya
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  2. Yu Chun-na
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  3. Xie Sheng-gu
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  4. Chen Shu-qing
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  5. Zeng Su
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Correspondence to Zeng Su.

Additional information

Project supported by the National Natural Science Foundation of China (No. 30225047) and the Science and Technology Foundation of Zhejiang Province, China (No. 2005C13026)

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You, Ly., Yu, Cn., Xie, Sg. et al. Stereoselective glucuronidation of carvedilol by Chinese liver microsomes. J. Zhejiang Univ. - Sci. B 8, 756–764 (2007). https://doi.org/10.1631/jzus.2007.B0756

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  • DOI: https://doi.org/10.1631/jzus.2007.B0756

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