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 mu g/kg over 5 min followed by 0. 1, 0.2, and 0.4 mu g/kg per min for 60 min, respectively) to 19 volunt eers. There were significant, dose related linear increases in QT and QT(c) intervals, in atrial functional and effective refractory periods (ERPs) at a paced cycle length of 400 ms, and in ventricular function al and ERPs at a paced cycle length of 600 ms. There was no significan t change in the AH and HV intervals or QRS duration. No significant pr oarrhythmic or other side effects were encountered during the administ ration of the drug. E 4031 prolongs atrial and ventricular refractorin ess 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 a nd well tolerated.