Electrophysiological evaluation of the sodium-channel blocker carbamazepine in healthy human subjects

Summary

Carbamazepine (CBZ) is a sodium-channel blocker used mainly for the treatment of epileptic seizures and neuralgias. It may impair the function of the cardiac conduction system in susceptible patients, but its electrophysiological effects have not been thoroughly assessed in the normal heart, which was the aim of the present study. Ten healthy volunteers, mean age 32 years, underwent two electrophysiological investigations at baseline and three at different dose levels of CBZ. The transesophageal atrial stimulation technique was used to evaluate sinus node function, refractoriness of the atrial myocardium, atrioventricular conduction, and ventricular depolarization and repolarization (as reflected by the QRS, JT, and QT intervals) at spontaneous rhythm and after atrial pacing. Atropine was administered to facilitate 1:1 conduction and assessment of rate-dependent effects. At the highest CBZ dose (800 mg/day), which gave plasma concentrations within the upper therapeutic range, the PQ interval was mildly prolonged (151 vs. 159 msec; p<0.01). In addition, the shortening of the JT interval normally seen at higher pacing rates was counteracted by high-dose CBZ, as demonstrated by a lower mean slope of the regression line after atropine and CBZ than after atropine alone (0.17 vs. 0.20; p<0.05). No other effects were detected. At therapeutic levels CBZ had minimal effects on the healthy conduction system, supporting its safe use in the absence of cardiac disease.