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 plasma concentrations of PA and N-acetylprocainamide (NAPA) as well as the pharmacodynamic effect (prolongation of the QT interval) were monitored. The PA plasma concentrations could be described by a one-compartment model with a t1/2 of 3.49 +/- 0.61 h. The total body clearance of PA was 0.395 +/- 0.090 l/hr/kg and the volume of distribution was 1.93 +/- 0.27 l/kg. As observed after PA administration, NAPA (an active metabolite) had a t1/2 longer than PA of 6.31 +/- 1.49 h. Peak NAPA concentrations (1.91 +/- 0.51 micrograms/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 acetylators. Percentage change in the QT interval was examined with respect to PA and PA + NAPA plasma concentrations. For PA, % delta QT = 41.2 log (PA) - 13.26 and correlations (r) ranged from 0.77 to 0.91 among the horses. In the case of PA+ NAPA, % delta QT = 57.3 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.