The pharmacokinetics and pharmacodynamics of procainamide in horses after intravenous administration

Abstract

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.

Sudden death of a horse with supraventricular tachycardia following oral administration of flecainide acetate

“…Digoxin treatment was maintained, and procainamide was added to the treatment protocol to cardiovert AT to sinus rhythm. The gelding received procainamide hydrochloride (2 g IV q 1 h for 7 doses; approximately 3 mg/kg) . No change of atrial rate and P′ wave morphology was documented after IV procainamide (combined with digoxin [0.4 mg IV, q 12 h; 0.0006 mg/kg]) compared to baseline although intermittent ventricular tachycardia with AV dissociation developed (Figure B).…”

Application of Computer-Assisted Radiotelemetry in the Pharmacokinetic and Pharmacodynamic Modeling of Procainamide and N-Acetylprocainamide

“…The effect versus I alone or I plus II plasma concentrations have been studied in humans and still remains a controversial issue in monitoring patient response. Recently, Ellis et al 27 evaluated the percentage change in QT interval with respect to I and I plus II plasma concentrations, however II did not reach therapeutic levels. Further, the addition of II did not significantly improve the relationship to the QT interval.…”

Reacciones adversas de los fármacos en los equinos

“…Su metabolito activo (N-acetilprocainamida) tiene una vida media más larga y se puede acumular después de dosis múltiples. 238,239 En pacientes con ICC se elevan las concentraciones plasmáticas de la procainamida y de la N-acetilprocainamida, o debido a una disminución en la excreción urinaria y a la hidrólisis sanguínea de la procainamina. 238 Su toxicidad se manifiesta por un alargamiento del intervalo QT mayor al 50%.…”

“…238 Su toxicidad se manifiesta por un alargamiento del intervalo QT mayor al 50%. 239 Además, se pueden presentar arritmias adicionales, bloqueo AV, bradicardia, taquicardia o hipotensión. 2,170…”

“…234 Hay además hipotensión, efectos cronotrópico e inotrópico negativos, ensanchamiento del complejo QRS, bloqueo cardiaco y paradójicamente, arritmias ventriculares. 96,239 Es muy importante que se verifique que la lidocaína no contenga epinefrina. Para administrar la lidocaína se aconseja utilizar solución salina o Ringer, pues otras soluciones poliiónicas son químicamente antagónicas.…”