Electrophysiological properties of mexiletine assessed with respect to plasma concentrations

Electrophysiological measurements were made before and after the intravenous administration of mexiletine in 14 patients with preexcitation syndromes. Following a single infusion of 3 mg/kg body weight plasma concentrations of mexiletine fell rapidly and after 15 min, significant changes in electrophysiological measurements were not found. Higher plasma mexiletine concentrations, bringing about a pharmacological effect, were attained when a second intravenous infusion was also given. The results suggest a minimum effective plasma concentration for mexiletine of about 0.5 mg/l. Side-effects were minimal and their production was largely dependent on the rate of drug infusion. Electrophysiological measurements in previous studies may have been made at a time when plasma mexiletine concentrations were below an effective level and this could explain a disparity in their findings.