A study to compare the efficacy, plasma concentration profile and tolerability of conventional mexiletine and slow-release mexiletine.
In order to evaluate and compare slow-release mexiletine 360 mg 12 hourly and conventional mexiletine 200 mg 8 hourly, twelve patients with symptomatic ventricular arrhythmias have been studied. Ambulatory electrocardiographic monitoring was performed before treatment and at the end of two, two week long treatment periods during which slow-release mexiletine and conventional mexiletine were administered in random order. On the last day of each treatment period frequent blood samples for drug assay were collected during a dosage interval. Each formulation produced greater than 70% suppression of ventricular ectopic beats in 55% of patients. The variation between pre-dose and observed peak plasma concentration was 29.6% with slow-release mexiletine and 71.6% with mexiletine (P less than 0.01). The time from pre-dose to observed peak concentration was 4.0 h (+/- 1.6 SD) with slow-release mexiletine and 2.0 h (+/- 1.8 SD) with conventional mexiletine (P less than 0.05). Three patients were withdrawn from the study in the first treatment period because of central nervous system or gastric adverse effects. Overall, side-effects were marginally fewer on therapy with slow-release mexiletine. We conclude that, in the nearest equivalent dosage, the slow-release formulation is as effective as conventional mexiletine and at least as well tolerated. The fluctuations in plasma mexiletine concentration are less marked on the slow-release preparation despite the longer dosage interval, which allows effective oral therapy with a twice daily dosage.
D000284:Administration, Oral; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000097:blood / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D004341:Drug Evaluation; D004562:Electrocardiography; D005260:Female; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008875:Middle Aged; D008991:Monitoring, Physiologic; D011437:Propylamines / Q000627:therapeutic use*; D011897:Random Allocation
D003692:Delayed-Action Preparations; D011437:Propylamines; D008801:Mexiletine