E 047/1: A new class III antiarrhythmic agent

The efficacy, pharmacokinetics, safely, and tolerability of E 047/1, an ami odarone derivative, were evaluated in patients with acute supraventricular or ventricular arrhythmia. In an open, nonrandomized prospective multicente r trial, 20 patients were treated with three different i.v. dosage regimens of E 047/1. Arrhythmia termination indicated efficacy. Pharmacokinetics we re determined by measurements of drug plasma levels. Safety was judged by c hanges of blood pressure, heart rate, ECG parameters, and appearance of adv erse events. For local tolerability, effects at the site of infusion were a ssessed. In patients with atrial fibrillation and/or atrial flutter, drug p lasma levels and prolongation of BT interval were correlated with efficacy. In 10 (50%) patients, therapeutic intervention with E 047/1 was successful . Drug plasma levels rapidly decreased within I h after administration. Blo od pressure values and ECG parameters stayed constant during the observatio n period. Proarrhythmic effects were nor observed. As adverse events, verti go, vomiting, and nausea in three (15%) and hypotension in one (5%) patient , respectively, occurred in the high-dose bolus regimen only. At the site o f infusion, no adverse effects were found. No dependency between drug plasm a levels and arrhythmia termination was found. E 047/1 has proven to be eff icient and safe in the treatment of arrhythmia. E 047/1 is characterized by rapid plasma elimination, absence of proarrhythmic or cardiodepressive eff ects, mild adverse events, and excellent local tolerability. For further in vestigation, we recommend a combined bolus- and weight-adapted infusion reg imen.