Baseline pharmacology, electrophysiology and pharmacokinetics of mexiletine.

Abstract

Mexiletine is effective in abolishing experimentally induced cardiac arrhythmias and belongs to the Vaughan-Williams Class I group of antiarrhythmic agents. It depresses the maximum rate of depolarisation with little or no modification of resting potentials or the duration of action potentials. When given intravenously mexiletine redistributes rapidly from plasma to tissues after a single intravenous injection. Therapeutic plasma concentrations lie in the region of 1-2 mcg/ml and in order to achieve these concentrations rapidly an initial loading dose is desirable. After oral administration it is rapidly and well adsorbed. An initial oral loading dose is advisable to achieve constant adequate plasma concentrations. The prior administration of opiates may delay oral absorption but this is compensated for by a larger initial loading dose. The half-life may vary under certain circumstances and lies in the region of 10-16 hours. Some 10-15% is excreted unchanged in the urine within 72 hours of oral administration. Mexiletine is largely metabolised in the liver and although there is some renal excretion with pH dependent tubular reabsorption, in clinical practice this has not presented any major problems.