Dose effect of moricizine on suppression of ventricular arrhythmias

To define the pharmacologic properties of moricizine in patients with benign or potentially lethal ventricular arrhythmias, 1,072 patients in the moricizine data base through February 1987 were evaluated. In dose-ranging and titration trials as well as in a cross-study analysis of th entire data base, the minimally effective dose for moricizine was found to be 600 mg/day and the optimal dose range from 600 to 900 mg/day. The dose efficacy relation plateaued beyond 900 mg/day. With use of a 75% reduction in ventricular premature complex frequency as the definition of a drug responder, 391 of 583 patients (67%) with paired Holter monitors demonstrated overall efficacy. The dose onset of moricizine was between 16 and 20 hours and the dose offset was at approximately 24 hours at the point when 50% of the ventricular arrhythmia frequency returned to baseline. Although moricizine was primarily given on a 3-times-a-day regimen during clinical trials, dose interval evaluation suggested that a twice-a-day regimen may produce the same degree of efficacy although there are limited data regarding comparable safety.