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The aim of this study was to compare the pharmacokinetics and antiarrhythmic activity of dihydroquinidine and quinidine in 14 patients (11 men, 3 women, aged 28 to 67 years) with heart disease and chronic, stable, highfrequency premature ventricular beats (PVB) (>100/hr). A randomized, double-blind, crossover, placebo-controlled protocol was utilized. During Holter monitoring the patients were given either dihydroquinidine or quinidine as the gluconates in an oral solution (600 mg); blood samples were taken 0.5, 1, 1.5, 2, 4, 6, 8, and 12 hours later. The patients were then assigned to three successive treatment periods of 7 days each: dihydroquinidine HCl (900 mg/day), quinidine polygalacturonate (1,650 mg/day), or placebo. At the end of each period 24-hour Holter monitoring was carried out and a blood sample was taken for determination of drug concentration. By comparing the area under the curves dihydroquinidine was 59% as available as quinidine; rates of absorption and elimination were similar. Mean peak blood levels of dihydroquinidine and quinidine were 1.06±0.34 and 2.15±0.96 μg/ml, respectively. After dihydroquinidine, eight patients had a positive response (>50% reduction in PVB frequency), while seven patients responded to quinidine. During maintenance treatment both dihydroquinidine (233±330) and quinidine (234±311) reduced the mean PVB frequency per hour compared to placebo (690±569). Nine patients (64%) on dihydroquinidine and eight (57%) on quinidine had >70% decrease in mean PVB frequency per hour. Steady-state peak plasma concentrations of dihydroquinidine and quinidine were 1.10±0.41 and 2.24±1.13 μg/ml, respectively. Dihydroquinidine thus has stronger antiarrhythmic activity than quinidine and so may be used in lower doses; it is effective with plasma concentrations lower than those of quinidine.