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  • Title: Correlation of the electrophysiological and antiarrhythmic properties of the N-acetyl metabolite of procainamide with plasma and tissue drug concentrations in the dog.
    Author: Bagwell EE, Walle T, Drayer DE, Reidenbert MM, Pruett JK.
    Journal: J Pharmacol Exp Ther; 1976 Apr; 197(1):38-48. PubMed ID: 1263131.
    Abstract:
    N-acetylprocainamide (NAPA), a major metabolite of procainamide (PA) in man, has been reported recently to be biologically active. The present 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 bath 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 mug/g) were significantly greater than those of PA (43+/-2 mug/g). Neither drug was metabolized by the fibers. In 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 to 60 mg/kg of PA. This difference in potency could not be attributed to differences in plasma and tissue concentrations of the drugs. These results show that NAPA is equally efficacious but less potent than PA as an antiarrhythmic drug in dogs.
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