摘要：The effects of nilvadipine, a dihydropyridine calcium antagonist, on cytochrome P450 (CYP) activities in human hepatic microsomes were investigated. Nilvadipine competitively inhibited CYP1A2-mediated 7-ethoxyresorufin O -deethylase, CYP2A6-mediated coumarin 7-hydroxylase, CYP2C8/9-mediated tolbutamide methylhydroxylase, CYP2C19-mediated S -mephenytoin 4′-hydroxylase, and CYP3A4-mediated nifedipine oxidase activities, and the inhibition constant ( K i) values were 13.0, 35.8, 5.02, 24.5 and 44.3 μ M , respectively. On the other hand, no inhibition of CYP2B6-mediated 7-benzyloxyresorufin O -debenzylation, CYP2D6-mediated bufuralol 1′-hydroxylation, or CYP2E1-mediated chlorzoxazone 6-hydroxylation by nilvadipine at 40 μ M concentration was observed. The free fractions of nilvadipine in the incubation mixture estimated by ultracentrifugation were 18.9—27.4%. These results suggest that nilvadipine would not cause clinically significant interactions with other drugs, which are metabolized by CYPs, via the inhibition of metabolism.
