Electrophysiologic effects, antiarrhythmic activity and pharmacokinetics of cibenzoline studied with programmed stimulation of the heart in patients with supraventricular reentrant tachycardias

Abstract

Cibenzoline, an imidazoline derivative is a new antiarrhythmic agent. Its electrophysiologicaleffects and antiarrhythmic properties were studied with programmed electrical stimulation of the heart in 12 patients with recurrent episodes of reentrant supraventricular tachycardia; atrionodal (5 cases), circus movement tachycardia involving an accessory pathway (6 cases), intraatrial reentry (one case). Cibenzoline was infused intravenously at a dose of 1 mg kg^-1 to 1.75 mg kg⁻¹ during sustained episodes of tachycardia and over 9 to 15 min. Cibenzoline shortened the sinus cycle length, moderately increased the transnodal conduction time and markedly lengthened the HV interval. The refractory periods of the atrioventricular (A–V) node, the atrium and the ventricle did not change. The effects of cibenzoline on accessory pathways used in the anterograde direction were measurable in 4 cases. Complete blockade of the bypass was seen in every case. In the retrograde direction the refractory period of the bypass could be evaluated; in 5 patients it lengthened systematically. Infused intravenously during epidoses of tachycardia, the drug terminated the rhythm disorder in 9 out of 12 cases. Tachycardia could still be initiated in 8 patients after i.v. cibenzoline (2 out of 5 A-V nodal tachycardias, 6 out of 6 circus movement tachycardias). The distribution of the drug followed a bicompartment pharmacokinetic model. The plasma levels at the end of infusion ranged from 1.34 to 3.19 μg ml⁻¹. Cibenzoline, primarily has class I antiarrhythmic properties and its well-understood pharmacokinetics should be of help in tailoring the treatment to the individual needs of the patient.