The mechanism of action of
moricizine, a new antiarrhythmic agent used in the
Cardiac Arrhythmia Suppression Trial, is incompletely characterized. In addition, because
moricizine is extensively metabolized, plasma
moricizine concentration has an unknown relation to myocardial
drug effect. Signal-averaged and standard electrocardiograms (ECGs) were used to monitor
moricizine's myocardial effects in 16 patients with frequent
ventricular premature complexes taking 600 to 900 mg daily. Three signal-averaged ECG variables were measured: total filtered QRS duration (fQRS), root-mean-square voltage in the terminal 40 ms of the QRS complex (V40) and the terminal low amplitude duration less than 40 microV (LAS). At steady state, plasma samples were collected and serial recordings of signal-averaged and standard ECGs were taken at 0, 1, 2, 4, 6 and 8 h after
moricizine administration. A 24 h ambulatory ECG was recorded throughout the test period.
Moricizine prolonged the fQRS (p less than 0.05) and decreased the V40 (p less than 0.05) of the signal-averaged ECG and prolonged the QRS (p less than 0.05) and corrected JT (JTc) intervals (p less than 0.05) of the standard ECG. The time course of the signal-averaged and standard ECG variables paralleled plasma
moricizine concentration; that is, the maximal changes occurred at 1 to 2 h and declined to time 0 values at 8 h. The maximal changes were: fQRS (+8%), V40 (-33%), QRS (+8%) and JTc (+4%). Thus, dynamic changes were observed for intraventricular conduction (fQRS, QRS) and ventricular repolarization (JTc) over the dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)