Cardiovascular actions and pharmacokinetics of desethyl-N- acetylprocainamide in the dog

JJ Lertora and LW King

The pharmacokinetic profile and the cardiovascular actions of desethyl- N-acetylprocainamide (NAPADE) were studied in chloralose-urethane anesthetized dogs. NAPADE was given as a 15-min i.v. infusion in doses of 12 and 60 mg/kg. In all cases, the plasma concentration vs. time curve could be resolved into two exponential components, and the distribution and elimination of NAPADE were analyzed with a two- compartmental model. Total apparent volume of distribution was 0.4153 +/- 0.0301 liters/kg (mean +/- S.E.M.) for the 12-mg/kg group and 0.4946 +/- 0.0691 liters/kg for the 60-mg/kg group (P greater than .05). Elimination clearance was 0.0061 +/- 0.0006 liters/min/kg for the 12-mg/kg group and 0.0086 +/- 0.0013 liters/min/kg for the 60-mg/kg group (P greater than .05). The elimination phase half-life (T1/2 beta) was 57.0 +/- 4.1 and 53.1 +/- 3.2 min for the 12- and 60-mg/kg groups, respectively (P greater than .05). Thus, NAPADE exhibited first-order kinetics of distribution and elimination in the dose range studied. Renal clearance of unchanged NAPADE amounted to 45.9 +/- 4% of total plasma clearance. NAPADE had a dose- and concentration-related positive inotropic effect, as measured with a Walton-Brodie gauge sutured to the right ventricle. A 12-mg/kg infusion caused a peak increased in myocardial force of 18.4 +/- 3.6% over base line, whereas a 60-mg/kg infusion caused a peak increase in myocardial force of 48.9 +/- 10% over base line. The positive inotropic effect of NAPADE was sustained for 50 to 90 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 238, Issue 3, pp. 893-899, 09/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics