Amlodipine inhibits rat microsomal cytochrome P450‐mediated drug biotransformation
Identifieur interne : 003C12 ( Main/Exploration ); précédent : 003C11; suivant : 003C13Amlodipine inhibits rat microsomal cytochrome P450‐mediated drug biotransformation
Auteurs : Robert K. Drobitch [Canada] ; Roman A. Mclellan [Canada, Suède] ; Kenneth W. Renton [Canada]Source :
- Journal of Pharmaceutical Sciences [ 0022-3549 ] ; 1997-12.
Abstract
Calcium channel antagonists have been shown to inhibit cytochrome P‐450‐mediated metabolism both in vitro and in vivo. The purpose of the present study was to examine the effect of amlodipine on a suite of rat hepatic microsomal cytochrome P‐450 activities to determine the potential for drug interactions. In this study, amlodipine (0.05 and 0.5 mM) decreased CYP1A‐mediated ethoxyresorufin O‐deethylase activity in microsomes prepared from noninduced (56 and 73% inhibition) and pyridine‐induced (30 and 51% inhibition) rats. Amlodipine reduced pentoxyresorufin O‐deethylase activity (a marker for CYP2B) to 15% of control in incubations utilizing microsomes from phenobarbital‐treated rats, but had no effect on this enzyme reaction in noninduced microsomes. The para‐nitrophenol hydroxylase, erythromycin N‐demethylase, and lauric acid ω and ω −1 hydroxylase activities were significantly inhibited by 1 mM amlodipine in both noninduced and induced microsomes. These results suggest that amlodipine inhibits a number of different P450 forms and therefore has the potential to inhibit the metabolism of a large number of drugs.
Url:
DOI: 10.1021/js970188t
Affiliations:
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The purpose of the present study was to examine the effect of amlodipine on a suite of rat hepatic microsomal cytochrome P‐450 activities to determine the potential for drug interactions. In this study, amlodipine (0.05 and 0.5 mM) decreased CYP1A‐mediated ethoxyresorufin O‐deethylase activity in microsomes prepared from noninduced (56 and 73% inhibition) and pyridine‐induced (30 and 51% inhibition) rats. Amlodipine reduced pentoxyresorufin O‐deethylase activity (a marker for CYP2B) to 15% of control in incubations utilizing microsomes from phenobarbital‐treated rats, but had no effect on this enzyme reaction in noninduced microsomes. The para‐nitrophenol hydroxylase, erythromycin N‐demethylase, and lauric acid ω and ω −1 hydroxylase activities were significantly inhibited by 1 mM amlodipine in both noninduced and induced microsomes. 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