[Absence of polymorphism in individual response to the dihydropyridines nifedipine and (+/-)-nicardipine].

Nifedipine, the dihydropyridine calcium channel antagonist prototype, is characterized by wide variability of its hepatic first-pass metabolism and individual response. This could be due to a new genetic polymorphism of drug metabolism, and this hypothesis was investigated in a randomized and cross-over population study in normal volunteers (n = 80). The kinetics and effects of an oral dose of nifedipine (10 mg) and (+/-)-nicardipine (20 mg), a second generation derivative with presumed different biotransformation routes, were evaluated at 0, 1, 2 and 3 h. The two drugs displayed a similar pharmacodynamic profile in terms of heart rate and blood pressure. The observed frequency distributions showed no asymmetry or bimodality suggesting polymorphism. The frequency of headaches and flushes were 21/80 and 19/80 respectively for nifedipine and (+/-)-nicardipine. At the doses administered nifedipine and (+/-)-nicardipine show the same efficacy. This study does not confirm the presence of polymorphism in the response to these dihydropyridines.