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, high-frequency
premature ventricular beats (PVB) (greater than 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 micrograms/ml, respectively. After
dihydroquinidine, eight patients had a positive response (greater than 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 greater than 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 micrograms/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)