CORRELATION OF ELECTROPHYSIOLOGICAL AND ANTIARRHYTHMIC PROPERTIES OF N-ACETYL METABOLITE OF PROCAINAMIDE WITH PLASMA AND TISSUE DRUG CONCENTRATIONS IN DOG

  • 1 January 1976
    • journal article
    • research article
    • Vol. 197  (1) , 38-48
Abstract
N-acetylprocainamide (NAPA), a major metabolite of procainamide (PA) in man, was reported recently to be biologically active. This study compares the electrophysiological and antiarrhythmic effects of NAPA and PA and correlates their activity with plasma and tissue drug concentrations. In isolated canine Purkinje fibers NAPA, in both concentrations of 10 and 20 mg/l, reduced automaticity and prolonged repolarization time. These effects were similar to those observed with similar concentrations of PA. Tissue concentrations of NAPA (77 .+-. 2 .mu.g/g) were significantly greater than those of PA (43 .+-. 2 .mu.g/g). Neither drug was metabolized by the fibers. In vivo studies NAPA (140-220 mg/kg) significantly suppressed the incidence of arrhythmias following coronary occlusion and digitalis intoxication. Similar protection was obtained with 40-60 mg/kg of PA. This differences in potency could not be attributed to differences in plasma and tissue concentrations of the drugs. NAPA is equally efficacious but less potent than PA as an antiarrhythmic drug in dogs.