Evaluation of the pharmacokinetic and pharmacodynamic interaction between quinidine and nifedipine.
Quinidine and nifedipine appear to be subject to metabolism by the same isozyme of cytochrome P-450. In addition, both drugs have been reported to alter the pharmacokinetics of other compounds. To investigate a potential interaction, 10 healthy subjects (five male, five female) received quinidine sulfate (200 mg orally), nifedipine (20 mg orally), or the combination of both drugs every 8 hours for 4 doses using a randomized, cross-over study design with a 2-week washout period between treatments. Drug concentration, heart rate, and mean arterial pressure were measured at frequent intervals after the final dose. Quinidine concentrations were unchanged by the co-administration of nifedipine. Nifedipine area under the curve (AUC0-8) increased 36.6% from 333 to 455 micrograms.hr/L (P < .05) after quinidine administration. Heart rate was significantly higher in the nifedipine-quinidine treatment at 0.5, 1.0, 1.5, and 2.0 hours when compared with either drug alone. The maximum increase in heart rate (17.9 beats/minute) occurred at 0.5 hours after nifedipine administration and was significantly correlated with serum concentrations at that time (r = .78). These results suggest that quinidine inhibits nifedipine metabolism, and this pharmacokinetic interaction results in enhanced pharmacologic response.
Bowles
S K
SK
Department of Pharmacy, Sunnybrook Health Science Centre, Toronto, Ontario, Canada.
Reeves
R A
RA
Cardozo
L
L
Edwards
D J
DJ
D000284:Administration, Oral; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D009543:Nifedipine / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics / Q000494:pharmacology; D011802:Quinidine / Q000493:pharmacokinetics / Q000494:pharmacology*
D009543:Nifedipine; D011802:Quinidine