Comparison of the effectiveness of dihydroquinidine and quinidine on ventricular ectopy after acute and chronic administration

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.