Antiarrhythmic plasma concentrations of mexiletine on canine ventricular arrhythmias

Antiarrhythmic effects of mexiletine were examined using three canine ventricular arrhythmia models--digitalis-, adrenaline-, and two-stage coronary ligation-induced arrhythmias. The minimum effective plasma concentration for each arrhythmia model was determined. Mexiletine suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by digitalis, adrenaline, 24-h coronary ligation, and 48-h coronary ligation were 1.8 +/- 0.6, 3.7 +/- 0.9, 1.9 +/- 0.3, and 2.2 +/- 0.4 micrograms/ml, respectively (mean +/- SD, n = 6-7). The concentration for adrenaline-induced arrhythmias was significantly higher than those for the other types of arrhythmias. Mexiletine had a hypotensive effect when it was given intravenously, but this effect was not observed when it was given orally. Oral mexiletine was also effective in suppressing the 24-h coronary ligation-induced arrhythmia. Mexiletine induced convulsions when higher doses were given. The correlations between the mexiletine plasma concentrations and its antiarrhythmic effects were not very strong, probably indicating individual variations in sensitivity to mexiletine.