Dose-ranging studies of clofilium, an antiarrhythmic quaternary ammonium

Clofilium, a new quaternary ammonium antiarrhythmic without apparent ganglion-blocking effect, was evaluated in 25 patients, 22 with a history of ventricular arrhythmias and three with paroxysmal supraventricular arrhythmias. The study, including programmed atrial and ventricular stimulation, was carried out before and after infusion of 20 to 240 micrograms/kg IV as a single dose. Continuous Holter monitoring was carried out the day before the study through the fourth day after study, and laboratory parameters were monitored for up to 2 wk. There were no changes in intra-atrial and intraventricular conduction times or in AH or HV intervals. There were increases in QT interval, atrial effective refractory period, and ventricular refractory period. The atrioventricular nodal effective refractory period was unchanged. No side effects were noted, nor were changes in blood pressure or laboratory parameters. Monitoring revealed no change in frequency of premature ventricular complexes between the 24 hr before drug infusion and the 96 hr thereafter. In one patient refractoriness of the His-Purkinje system was increased and in two patients atrial fibrillation converted to sinus rhythm after clofilium. Three patients had sustained ventricular tachycardia with programmed stimulation before clofilium infusion; none had more than three repetitive ventricular responses after it. Clofilium increases atrial and ventricular effective refractory period without changing conduction time and, despite no apparent change in premature ventricular complex frequency, it can abolish the ability to induce ventricular tachycardia by programmed stimulation and is also well tolerated.