Absorption and antiarrhythmic efficacy of sustained-release mexiletine.

Absorption of the antiarrhythmic agent mexiletine from conventional capsules (200 mg) and two sustained-release formulations (360 and 432 mg) was studied in four healthy volunteer subjects, and use of the 360-mg preparation was studied in nine patients who had been using conventional capsules. In the four volunteers, acute dosage with the 432-mg preparation produced a markedly lower peak mexiletine concentration and fewer side effects than did two 200-mg capsules. Chronic dosing in two volunteers, which indicated that the 360-mg preparation produced fewer side effects and lower predose and peak plasma mexiletine concentrations than did the 432-mg preparation, suggested the use of equivalent doses of the 360-mg preparation in the nine patients who had been using 100-, 200-, or 250-mg preparations. The arrhythmia control produced by the slow-release preparation, as measured by 24-hour ECGs, was comparable to that produced by the conventional forms of mexiletine; gastrointestinal side effects were less marked when patients took the slow-release preparation, despite higher mean predose plasma mexiletine concentrations associated with use of the 360-mg preparation. Reduced frequency of daily dosage as well as patient acceptance are clinical advantages of the slow-release preparation.