Mexiletine, a class lb antiarrhythmic agent, is an orally active lidocaine analog. Its electrophysiologic profile and its lack of cardiac depressant activity are characteristic of this class of antiarrhythmic drugs. A long terminal-phase half-life, ranging from about 9 h in normal volunteers to 10 to 15 h in patients with arrhythmias, allows mexiletine to be administered for maintenance therapy at 8-h intervals.
In controlled comparative studies with quinidine and procainamide as well as in several placebo- controlled trials, mexiletine administered orally every 8 h effectively suppressed ventricular extrasys- toles. In pharmacokinetic studies, therapeutic plasma levels of mexiletine were maintained by oral administration of 200 to 300 mg every 6 to 8 h. Daily doses required for the control of ventricular arrhythmias have varied between 300 and 1,200 mg.
The present study was designed to determine whether the comparatively long elimination half-life of mexiletine would allow ventricular arrhythmias to be controlled as effectively and continually by 12-h as by 8-h administration in patients whose ventricular arrhythmias were first controlled with 8-h mexiletine therapy.