[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.
Porchet
H C
HC
Unité de pharmacologie clinique, Hôpital cantonal universitaire, Genève.
Benveniste
C
C
Adler
D
D
Dayer
P
P
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009529:Nicardipine / Q000493:pharmacokinetics*; D009543:Nifedipine / Q000493:pharmacokinetics*; D011110:Polymorphism, Genetic; D011897:Random Allocation; D013997:Time Factors
D009529:Nicardipine; D009543:Nifedipine
Absence de polymorphisme dans la réponse individuelle aux dihydropyridines nifédipine et (+/-)-nicardipine.