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 Three patients were withdrawn from the study in the first treatment period because of central nervous system or gastric adverse effects.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.