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.
University of Medicine and Pharmacy Carol Davila, Bucharest, Romania.
V
V
Voicu
C
C
Mircioiu
M
M
Jinga
M
M
Ionescu
X
X
Burcea
D D
DD
Ionescu
G
G
Lupescu
D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy*; D002849:Chromatography, Gas; D016757:Death, Sudden, Cardiac / Q000517:prevention & control; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D006801:Humans; D007273:Injections, Intramuscular; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009203:Myocardial Infarction / Q000517:prevention & control
D003692:Delayed-Action Preparations; D008012:Lidocaine