2008
DOI: 10.1248/bpb.31.1297
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Stereoselective Oxidation and Glucuronidation of Carvedilol in Human Liver and Intestinal Microsomes

Abstract: The aim of the present study was to investigate the mechanism for the stereoselective presystemic clearance of carvedilol. We examined the oxidation and glucuronidation of carvedilol in human liver microsomes (HLM) and human intestinal microsomes (HIM). The oxidation of carvedilol in HLM and HIM was evaluated in the presence of NADPH, whereas glucuronidation was evaluated in the presence of UDP-glucuronic acid. Oxidation of S-carvedilol in HLM and HIM was greater than that of R-carvedilol. In addition, the oxi… Show more

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Cited by 29 publications
(34 citation statements)
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“…According to previous reports, the concentration of CYP-specific inhibitors was determined as follows: 25 mM furafylline (inhibitor of CYP1A2), 10 mM sulfaphenazole (inhibitor of CYP2C9), 1 mM quinidine (inhibitor of CYP2D6), and 1 mM ketoconazole (inhibitor of CYP3A4). 9,10) The concentrations of amiodarone (50 mM) and desethylamiodarone (25 mM) were determined according to the report of Ohyama et al 13) In the pooled HLM (#18888), the oxidation activity for Rcarvedilol was significantly decreased by quinidine (to 49.7% of control), whereas that for S-carvedilol was decreased by furafylline (to 70.6% of control). The results reconfirmed that CYP2D6 and CYP1A2 in the pooled HLM contributed mainly to the oxidation of R-and S-carvedilol, respectively.…”
Section: Resultsmentioning
confidence: 99%
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“…According to previous reports, the concentration of CYP-specific inhibitors was determined as follows: 25 mM furafylline (inhibitor of CYP1A2), 10 mM sulfaphenazole (inhibitor of CYP2C9), 1 mM quinidine (inhibitor of CYP2D6), and 1 mM ketoconazole (inhibitor of CYP3A4). 9,10) The concentrations of amiodarone (50 mM) and desethylamiodarone (25 mM) were determined according to the report of Ohyama et al 13) In the pooled HLM (#18888), the oxidation activity for Rcarvedilol was significantly decreased by quinidine (to 49.7% of control), whereas that for S-carvedilol was decreased by furafylline (to 70.6% of control). The results reconfirmed that CYP2D6 and CYP1A2 in the pooled HLM contributed mainly to the oxidation of R-and S-carvedilol, respectively.…”
Section: Resultsmentioning
confidence: 99%
“…9) That is, the incubation mixture (final volume 100 ml) consisted of 1 mM racemic carvedilol, 1.0 mg/ml microsomal proteins, 2 mM NADPH, and 50 mM potassium phosphate buffer (pH 7.4). Carvedilol was dissolved in a mixture of dimethylformamide and acetonitrile, and the final concentrations of dimethylformamide and acetonitrile in the mixture were 0.05% and 0.02% (v/v), respectively.…”
Section: Methodsmentioning
confidence: 99%
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