EVALUATION OF THE PHARMACOKINETIC AND PHARMACODYNAMIC INTERACTION BETWEEN QUINIDINE AND NIFEDIPINE

Quinidine and nifedipine appear to be subject to metabolism by the some 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 mug . 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.