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
em En
| WPRIM
| ID: wpr-277333
Biblioteca responsável:
WPRO
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>
Texto completo:
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Base de dados:
WPRIM
Assunto principal:
Propanolaminas
/
Estereoisomerismo
/
Microssomos Hepáticos
/
Carbazóis
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China
/
Ácido Glucurônico
/
Glucuronídeos
/
Metabolismo
País/Região como assunto:
Asia
Idioma:
En
Revista:
Journal of Zhejiang University. Science. B
Ano de publicação:
2007
Tipo de documento:
Article