Electrophysiologic effects of cibenzoline in humans related to dose and plasma concentration.
The electrophysiologic effects of a new antiarrhythmic agent, cibenzoline, were investigated in 25 patients with an average age of 62 years. The compound was administered intravenously, as a bolus given over 2 minutes, then as a slow infusion over 40 minutes. Each subject was randomly allocated to receive one of the following four doses: 1.55 mg/kg (six patients), 1.8 mg/kg (six patients), 2.2 mg/kg (six patients), or 2.6 mg/kg (seven patients). Plasma cibenzoline concentrations at these doses were 378 +/- 80,525 +/- 194, 618 +/- 72, and 731 +/- 196 ng/ml, respectively. Administration of 1.55 mg/kg cibenzoline significantly shortened the sinus cycle (60 msec on average; p less than 0.025) and increased intraatrial (+8 msec; p less than 0.05) and His-Purkinje conduction times (HV interval + 13 msec; p less than 0.001). At 1.80 mg/kg, prolongation occurred in the HV interval (+9 msec; p less than 0.02), the duration of the QRS complex (+20 msec; p greater than 0.05), and the QT interval (+18 msec; p less than 0.025). At the higher doses these changes became more marked (maximum increase: HV = +16 msec, p less than 0.001; QRS + 25 msec; p less than 0.001; QT + 26 msec, p less than 0.05), and additional effects on atrioventricular nodal conduction time (AH interval + 17 msec; p less than 0.05) and atrial (+20 msec; p less than 0.05) and ventricular (+10 msec; p greater than 0.05) effective refractory periods were observed. Prolongation of the QRS duration was the effect that correlated best with plasma cibenzoline levels (r = 0.47; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D002986:Clinical Trials as Topic; D004562:Electrocardiography; D004594:Electrophysiology; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D011897:Random Allocation; D012849:Sinoatrial Node / Q000187:drug effects; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; C032151:cifenline