Quinidine interaction with nifedipine and felodipine: pharmacokinetic and pharmacodynamic evaluation.
Conflicting findings suggest that serum quinidine concentrations may be decreased or increased by nifedipine. We performed a double-blind, placebo-controlled trial of Latin-square design. Twelve healthy men received 3 days of pretreatment with nifedipine prolonged action (20 mg twice a day) or felodipine extended release (10 mg every day), another dihydropyridine calcium antagonist, followed by coadministration of quinidine (400 mg). Quinidine pharmacokinetics were not changed by either dihydropyridine. However, 3-hydroxyquinidine area under the concentration-time curve (AUC) and 3-hydroxyquinidine/quinidine AUC ratio were decreased by felodipine, consistent with reduced metabolite formation. Heart rates and adverse events were higher with felodipine, demonstrating lack of bioequivalence with nifedipine. The QTc interval did not deviate from that expected for the observed quinidine concentration, suggesting the pharmacokinetics of active quinidine metabolites were not markedly altered among treatments. Quinidine disposition did not appear to be changed sufficiently to be clinically important by sustained-release nifedipine and felodipine.
Bailey
D G
DG
Department of Medicine, Victoria Hospital, London, Ontario, Canada.
Freeman
D J
DJ
Melendez
L J
LJ
Kreeft
J H
JH
Edgar
B
B
Carruthers
S G
SG
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004347:Drug Interactions; D015736:Felodipine / Q000009:adverse effects / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000009:adverse effects / Q000494:pharmacology*; D011802:Quinidine / Q000009:adverse effects / Q000493:pharmacokinetics*; D012016:Reference Values; D012044:Regression Analysis
D003692:Delayed-Action Preparations; D009543:Nifedipine; D011802:Quinidine; D015736:Felodipine