Effect of cimetidine on the pharmacokinetics and pharmacodynamics of quinidine

The influence of Cimetidine (1.2 g/day for 7 days) on the disposition and pharmacodynamic effects of a single oral dose of qulnidine was studied in 6 normal volunteers. Cimetidine reduced the mean apparent oral clearance of quinidine (± standard error of the mean) from 25.5 ± 2.7 to 16.2 ± 1.4 liters/h (p < 0.05). This was reflected in a 55% (range 30 to 109) increase in the mean half-life from 5.8 ± 0.2 to 9.0 ± 0.6 hours (p < 0.05). Peak quinidine plasma concentrations and times to peak were also increased (p < 0.05). Plasma protein binding and urinary excretion of quinidine were unchanged by Cimetidine treatment. Alterations in the pharmacokinetic variables of quinidine were mirrored in simultaneously measured electrocardiographic parameters. Changes in Q-T, rate-corrected Q-T, QRS, and R-R intervals after a single oral dose of quinidine sulfate (400 mg) were significant. Treatment with cimetidine potentiated these pharmacodynamic changes, but failed to achieve significant differences from quinidine alone. Thus, cimetidine impairs the elimination of oral quinidine in normal volunteers. This interaction may lead to quinidine toxicity in patients in whom Cimetidine is concomitantly administered.