THERAPY AND PREVENTION ARRHIYTH[MIA Comparison of the electrophysiologic effects of intravenous and oral lorcainide in patients with recurrent ventricular tachycardia

The electrophysiologic effects of intravenous lorcainide (2.2 mg/kg) in 10 patients were compared with the electrophysiologic effects of oral lorcainide (mean dose 400 mg/day for 8 days) in 11 patients, all with recurrent ventricular tachycardia that could be induced with programmed stimulation. Intravenous and oral lorcainide resulted in similar prolongation of the QRS, QT, and HV intervals, but only oral lorcainide resulted in prolongation of the AH interval and atrial and ventricular effective refractory periods. After both oral and intravenous lorcainide, ventricular tachycardia could still be induced, but the arrhythmia was slower and better tolerated hemodynamically. The mean plasma lorcainide level during a maintenance intravenous infusion was 1254 + 662 ng/ml compared with a lorcainide level of 562 41 ng/ml and a norlorcainide level of 1212 + 653 ng/ml after oral dosing. No norlorcainide was detected in plasma after intravenous lorcainide. These data suggest that the shortterm electrophysiologic effects of intravenous lorcainide may be different from those of short-terrn therapy with the oral drug. These differences should be considered during short-term studies of lorcainide. Circulation 68, No. 2, 392-399, 1983. LORCAINIDE is a new antiarrhythmic drug that decreases the rate of rise of phase 0 of the cardiac intracellular action potential, and the conduction velocity, spontaneous activity, and effective refractory period in isolated dog Purkinje fibers, dog papillary muscles, and guinea pig auricles. I Lorcainide is clinically effective in the treatment of premature ventricular contractions, reciprocating supraventricular tachycardia using an accessory pathway, and ventricular tachycardia.2Previous studies have described the electrophysiologic effects of intravenous lorcainide in man, and several of these have included data on the effect of the drug on the inducibility of ventricular tachycardia.i-' In contrast to the large amount of data available describing the electrophysiologic effects of intravenous lorcainide, there are only limited data on the oral drug. During longterm oral therapy a metabolite, norlorcainide, accumulates to plasma concentrations approximately two From the Cardiology Division, Department of Medicine, Stanford University Medical School, Stanford. Supported in part by Janssen Pharmaceutical. Address for correspondence: Debra S. Echt, M.D., Cardiology Division, Stanford University Medical Center, Stanford, CA 94305. Received Feb. 9, 1983; revision accepted April 14, 1983. *Present address: Cardiology Division, Foothills Hospital, 1403-29 NW, Calgary, Alberta, Canada T2N2TR. 392 times those of lorcainide. 8, 9 Norlorcainide has been administered to a single patient and was found to suppress chronic premature ventricular complexes.'0 In dogs, norlorcainide has electrophysiologic activity similar to that of lorcainide"; however, its effects in man are unknown. If the electrophysiologic effects of norlorcainide differ from those of lorcainide, as has been implied for encainide and its metabolites,'2 this would have important implications regarding the therapeutic testing and management of patients on oral compared with those on intravenous lorcainide. In this study, we have compared the clinical electrophysiologic effects of lorcainide during short-term intravenous administration with those observed during short-term oral therapy in two similar groups of patients with recurrent ventricular tachycardia.