Electrophysiological Effects of E 4031, a Drug with Selective Class III Properties, in Man

We studied the electrophysiological effects of E 4031, given in a dose ascending manner (1.5, 3.0, and 6.0 micrograms/kg over 5 min followed by 0.1, 0.2, and 0.4 microgram/kg per min for 60 min, respectively) to 19 volunteers. There were significant, dose related linear increase in QT and QTc intervals, in atrial functional and effective refractory periods (ERPs) at a paced cycle length of 400 ms, and in ventricular functional and ERPs at a paced cycle length of 600 ms. There was no significant change in the AH and HV intervals or QRS duration. No significant proarrhythmic or other side effects were encountered during the administration of the drug. E 4031 prolongs atrial and ventricular refractoriness without significantly affecting AV or intraventricular conduction, consistent with selective Class III properties. At the doses used in the present study, intravenous infusion of E 4031 appears to be safe and well tolerated.