THE PHARMACOKINETICS AND PHARMACODYNAMICS OF PROCAINAMIDE IN HORSES AFTER INTRAVENOUS ADMINISTRATION

Six horses were administered either 15 or 20 mg/kg body weight (b.w.) procainamide (PA) as an intravenous (i.v.) dose over 10 min. The plasm a concentrations of PA and N-acetylprocainamide (NAPA) as well as the pharmacodynamic effect (prolongation of the QT interval) were monitore d. The PA plasma concentrations could be described by a one-compartmen t model with a t1/2 of 3.49 +/- 0.61 h. The total body clearance of PA was 0.395 +/- 0.090 1/hr/kg and the volume of distribution was 1.9 3 +/- 0.2 7 1/kg. As observed after PA administration, NAPA (an active m etabolite) had a t1/2 longer than PA of 6.31 +/- 1.49 h. Peak NAPA con centrations (1.91 +/- 0.51 mug/ml) occurred at 5.2 h after the PA i.v. dose. The ratio of area under the curves for NAPA to PA was 0.46 +/- 0.15 which is similar to that expected in humans classified as slow ac etylators. Percentage change in the QT interval was examined with resp ect to PA and PA + NAPA plasma concentrations. For PA, %DELTAQT = 41.2 log (PA) -13.26 and correlations (r) ranged from 0.77 to 0.91 among t he horses. In the case of PA + NAPA, %DELTAQT = 5 7.3 log (PA + NAPA) -31.83 and ranged from 0.77 to 0.90. No evidence of toxicity was noted with respect to changes in the PR interval.