The electrophysiologic effects of oral cibenzoline

Five male patients with chronic stable ventricular arrhythmias underwent a placebo controlled ascending dose study with oral cibenzoline, a new type 1 antiarrhythmic drug. Ambulatory ECG (Holter) recordings and electrophysiologic studies were done while on placebo and on the maximum dose of cibenzoline. Drug toxicity, manifested by vomiting and QRS widening, accompanied by very high serum cibenzoline concentrations, was seen in two patients. A major reduction (greater than 85% in ventricular premature beats occurred in three patients including two in whom only relatively low serum concentrations had been achieved. Cibenzoline caused significant increases in AH (97 +/- 26 vs. 110 +/- 23 msec, p less than 0.01) and HV (59 +/- 7 vs. 78 +/- 7 msec, p less than 0.02), a major but statistically not significant increase in QRS (99 +/- 12 vs. 128 +/- 27 msec, NS) but QT (38 +/- 2 vs. 38 +/- msec) and QTc (42 +/- 1 vs. 44 +/- 3 msec) were essentially unchanged, even in toxic patients. Cibenzoline had no consistant effect on sinus cycle length, sinus node recovery time, or the relative, functional or effective refractory periods of the atrium and AV node. We conclude that cibenzoline has potent type 1 effects in prolonging HV but may be unique in not affecting QT or QTc, even at toxic levels. Its effects upon AH were unexpected and warrant further study.