PHARMACOKINETIC BASED ADJUSTMENT OF LIDOCAINE ANTIARRHYTHMIC SCHEDULE

Administration of lidocaine, 200 mg/day i.m. or 275 mg orally, decreas ed sudden death after myocardial infarct (from 20.7% to 10.3%) althoug h such schedules are not considered adequate to guarantee efficient pl asma levels. Inclusion of lidocaine in a polyethylene matrix assured a slow release and complete disappearance of known side effects. Lidoca ine was administered 200 mg intramuscularly to hospitalized patients e very 6 h or 275 mg oral tablets to healthy volunteers every 8 h and pl asma levels evaluated. Plasma levels after oral administration to heal thy 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 patien ts, plasma levels slowly increased with time, but clinical signs indic ated, in some cases, a much more rapid accumulation. The therapeutic e fficiency at low repeated doses was explained as a consequence of a sl ow accumulation on the one hand and of the addition of the action of M EGX, the major metabolite of lidocaine, on the other hand.