Evaluation of the Pharmacokinetic and Pharmacodynamic Interaction Between Quinidine and Nifedipine

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Abstract
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 μg · 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.