Premium
Quinidine interaction with nifedipine and felodipine: Pharmacokinetic and pharmacodynamic evaluation
Author(s) -
Bailey David G,
Freeman David J,
Melendez Libardo J,
Kreeft John H,
Edgar Boo,
Carruthers S George
Publication year - 1993
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1993.32
Subject(s) - quinidine , felodipine , nifedipine , dihydropyridine , pharmacology , pharmacokinetics , active metabolite , chemistry , metabolite , drug interaction , antagonist , medicine , calcium , receptor , blood pressure
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 QT c 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. Clinical Pharmacology and Therapeutics (1993) 53, 354–359; doi: 10.1038/clpt.1993.32