Pharmacokinetic based adjustment of lidocaine antiarrhythmic schedule

Administration of lidocaine, 200 mg/day i.m. or 275 mg orally, decreased sudden death after myocardial infarct (from 20.7% to 10.3%) although such schedules are not considered adequate to guarantee efficient plasma levels. Inclusion of lidocaine in a polyethylene matrix assured a slow release and complete disappearance of known side effects. Lidocaine was administered 200 mg intramuscularly to hospitalized patients every 6 h or 275 mg oral tablets to healthy volunteers every 8 h and plasma levels evaluated. Plasma levels after oral administration to healthy volunteers showed a great variability, so that it was not possible to draw a statistically significant conclusion about the accumulation of lidocaine in a period of 1 week. In coronary artery disease patients, plasma levels slowly increased with time, but clinical signs indicated, in some cases, a much more rapid accumulation. The therapeutic efficiency at low repeated doses was explained as a consequence of a slow accumulation on the one hand and of the addition of the action of MEGX, the major metabolite of lidocaine, on the other hand.