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.
Publication Date: 1994-08-01 PubMed ID: 7525982DOI: 10.1111/j.1365-2885.1994.tb00243.xGoogle Scholar: Lookup
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- Journal Article
Summary
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The research study explores the behavior (pharmacokinetics) and the effects (pharmacodynamics) of a drug called procainamide (PA), when given intravenously to horses. The study examined the changes in PA concentration in plasma over time, how it was distributed and eliminated in the body. It also analysed the effects of PA and its metabolite N-acetylprocainamide (NAPA) on the QT interval, which is an aspect of the horse’s heart rhythm.
Study Methodology
- Six horses received either 15 or 20 mg/kg body weight (b.w.) of procainamide (PA) through an intravenous (IV) dose over a period of 10 minutes.
- The concentrations of PA and its active metabolite N-acetylprocainamide (NAPA) in the horse’s blood plasma, as well as the pharmacodynamic effect (elongation of the heart’s QT interval), were monitored over time.
Pharmacokinetic Findings
- PA plasma concentrations followed a one-compartment model, i.e., the drug’s concentration in the blood plasma is assumed to decline linearly over time. The half-life (t1/2), an indicator of how quickly the drug concentration falls, was found to be about 3.5 hours.
- The body clearance of PA, which points to the rate at which the drug is eliminated from the organism, was calculated to be around 0.4 L/hour/kg. This indicates that the body of the horses was disposing of the drug at a moderate pace.
- The volume of distribution of PA, indicating how widely the drug had dispersed throughout the horse’s body, was found to be approximately 2 L/kg. It suggests a widespread distribution of the drug in the horse’s body.
- NAPA, the active metabolite of PA, had a longer half-life around 6.3 hours. Highest NAPA concentrations were observed approximately 5.2 hours after the PA was administered.
- The ratio between the concentrations of NAPA and PA was close to 0.46, indicating that the horses in the trial metabolized PA into NAPA at a rate similar to “slow acetylators” in human patients.
Pharmacodynamic Findings
- The study revealed that both PA and PA+ NAPA concentrations correlated with a change in the QT interval on the horses’ electrocardiograms. QT interval measures the time between the start of the Q wave and the end of the T wave in the heart’s electrical cycle. The prolongation suggests a slowing down of electrical conduction in the heart.
- No evidence of toxicity or adverse effects was observed from the drug administration, indicating that the doses used were safe for the horses.
Cite This Article
APA
Ellis EJ, Ravis WR, Malloy M, Duran SH, Smyth BG.
(1994).
The pharmacokinetics and pharmacodynamics of procainamide in horses after intravenous administration.
J Vet Pharmacol Ther, 17(4), 265-270.
https://doi.org/10.1111/j.1365-2885.1994.tb00243.x Publication
Researcher Affiliations
- Department of Pharmacal Science, School of Pharmacy, College of Veterinary Medicine, Auburn University, Alabama 36849.
MeSH Terms
- Acecainide / blood
- Animals
- Electrocardiography / veterinary
- Fluorescence Polarization Immunoassay / veterinary
- Half-Life
- Heart / drug effects
- Horses / metabolism
- Infusions, Intravenous / veterinary
- Procainamide / pharmacokinetics
- Procainamide / pharmacology
Citations
This article has been cited 1 times.- Palmisano M, Leduc L, Avison A, Rassler S, Hopster K, Slack J. Transcutaneous electrocardioversion for treatment of atrial fibrillation and congestive heart failure in a Nubian wether. Can Vet J 2025 Aug;66(8):874-882.
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