title: Amlodipine inhibits rat microsomal cytochrome P450-mediated drug biotransformation.
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 omega and omega-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.
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: R K
authors.initials: RK
authors.lastname: Drobitch
authors.forename: R A
authors.initials: RA
authors.lastname: McLellan
authors.forename: K W
authors.initials: KW
authors.lastname: Renton
mesh_terms: D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D065607:Cytochrome P-450 Enzyme Inhibitors; D007527:Isoenzymes; D017311:Amlodipine