Quinidine single dose pharmacokinetics and pharmacodynamics are unaltered by omeprazole

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Abstract
Omeprazole has been shown in previous studies to inhibit the hepatic metabolism of selected drugs. Quinidine is an antiarrhythmic and antimalarial agent with a low therapeutic index. We therefore examined the effect of 40 mg omeprazole daily for one week or placebo on the pharmacokinetics and pharmacodynamics of a single 400 mg dose of quinidine in 8 healthy volunteers in a double-blind crossover study. During placebo and omeprazole treatment, there was no significant difference in area under the time-plasma quinidine concentration curve, (17.0 +/- 4.83 micrograms.h/ml, 18.6 +/- 4.43 micrograms.h/ml, respectively; P greater than 0.2) or renal clearance of quinidine (56.2 +/- 26.0 ml/min, 55.6 +/- 12.7 ml/min, respectively; P greater than 0.5). Quinidine unbound fraction in plasma (0.170 +/- 0.041 vs. 0.166 +/- 0.041 in the presence of omeprazole; P greater than 0.5) was not altered by omeprazole. Peak plasma quinidine concentration and the time this occurred did not differ. Omeprazole also had no effect on these parameters for the metabolite 3-hydroxyquinidine. There was no significant difference in the change in the corrected Q-T interval on the electrocardiogram due to quinidine (mean area under the time versus delta Q-Tc curve = 351 +/- 192 ms.h, placebo; 414 +/- 303 ms.h, omeprazole) showing that quinidine pharmacodynamics were unaltered by omeprazole. We conclude that omeprazole does not affect the pharmacokinetics of quinidine.