Key result
Co-administration of quinidine increased nifedipine AUC by 36.6% (from 333 to 455 micrograms.hr/L; P<0.05) and significantly increased heart rate compared with either drug alone.
Why the study?
Does the co-administration of quinidine and nifedipine alter drug concentrations and hemodynamic responses in healthy subjects?
RCT (n=10)
cross-over
Does the co-administration of quinidine and nifedipine alter drug concentrations and hemodynamic responses in healthy subjects?
Quinidine inhibits nifedipine metabolism, resulting in increased nifedipine exposure and an enhanced heart rate response.
Answers are grounded in this paper and cite their sources.
Potential interaction merits monitoring in co-prescription; leaves open confirmation in patients.
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.
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Bowles et al. (1993) conducted an RCT in Healthy subjects (n=10). Quinidine sulfate and nifedipine combination vs. Quinidine sulfate alone or nifedipine alone was evaluated on Nifedipine area under the curve (AUC0-8) (36.6% increase, p=< .05). Co-administration of quinidine increased nifedipine AUC by 36.6% (from 333 to 455 micrograms.hr/L; P<0.05) and significantly increased heart rate compared with either drug alone.
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