Serum concentrations and effects of (+/-)-nicardipine compared with nifedipine in a population of healthy subjects.
The dihydropyridine calcium antagonist (+/-)-nicardipine shares some of the pharmacologic properties of the dihydropyridine prototype nifedipine. To compare them, serum concentrations and cardiovascular effects of 10 mg nifedipine and 20 mg (+/-)-nicardipine were evaluated at 1, 2, and 3 hours after oral intake in a randomized, crossover, single-blind study involving 79 healthy volunteers. (+/-)-Nicardipine serum concentrations were much lower than those of nifedipine, indicating a greater hepatic first-pass metabolism of (+/-)-nicardipine. There was a significant correlation between serum concentrations of both drugs. The frequency distributions of nifedipine and (+/-)-nicardipine AUC (0-3), heart rate increase, and mean arterial pressure decrease showed no bimodality. This does not confirm the proposed polymorphism of nifedipine oxidation. Concentration-effect plots indicate that (+/-)-nicardipine is more potent than nifedipine but shows comparable efficacy in blood pressure reduction.
Porchet
H C
HC
Department of Medicine, University Hospital, Geneva, Switzerland.
Dayer
P
P
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D009529:Nicardipine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D009543:Nifedipine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D011110:Polymorphism, Genetic; D016032:Randomized Controlled Trials as Topic; D012016:Reference Values; D016037:Single-Blind Method
D009529:Nicardipine; D009543:Nifedipine