Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active metabolite m-chlorophenylpiperazine in the horse.
Abstract: Trazodone is a serotonin receptor antagonist and reuptake inhibitor used extensively as an anxiolytic in human and small animal veterinary medicine. The aims of this study were to determine the pharmacokinetics of oral trazodone in experimental horses and to evaluate the effect of oral trazodone in clinical horses. Six experimental horses were administered trazodone at 7.5 or 10 mg/kg. Plasma concentrations of trazodone and its metabolite (m-CPP) were determined via UPLC-MS/MS. Noncompartmental pharmacokinetic analysis, sedation and ataxia scores were determined. Trazodone was rapidly absorbed after oral administration with a maximum concentration of 2.5-4.1 μg/ml and half-life of the terminal phase of approximately 7 hr. The metabolite was present at low levels in all horses, representing only 2.5% of the total area under the curve. In experimental horses, concentration-dependent sedation and ataxia were noted, lasting up to 12 hr. For clinical cases, medical records of horses treated with trazodone for various abnormal behaviours were reviewed and data were summarized. Trazodone was successful in modifying behavioural problems to some degree in 17 of 18 clinical cases. Tolerance and subsequent lack of drug effect occurred in two of 18 clinical cases following 14 or 21 days of use. In both populations of horses, adverse effects attributed to trazodone include oversedation, muscle fasciculations and transient arrhythmias.
© 2018 John Wiley & Sons Ltd.
Publication Date: 2018-01-14 PubMed ID: 29333613PubMed Central: PMC7167085DOI: 10.1111/jvp.12477Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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The research article investigates the effects, behaviors, and clinical uses of a drug named Trazodone in horses. The drug, widely used as an anxiolytic in human and small animal treatment, was administered orally to selected horses to measure its absorption level, influence, side effects, and potential use in amending abnormal equine behavior.
Methodology and Experimentation
- Experiments were performed on six horses. The study administered the horses with Trazodone doses ranging from 7.5 to 10 mg/kg.
- The drug’s absorption was gauged by analyzing plasma concentrations of trazodone and its metabolite, m-CPP, via Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS).
- Assessments were also made on the sedation and ataxia (loss of full control of body movements) scores to determine the drug’s impact.
Findings
- The research found that Trazodone is rapidly absorbed after oral administration, reaching a maximum concentration of 2.5-4.1 μg/ml, with the terminal phase half-life being about 7 hours.
- The metabolite, m-CPP, appeared at low levels in all horses, contributing only 2.5% of the total exposure as measured by the area under the curve.
- In the experimental horses, the sedation and ataxia effects were correlated with the drug concentration, and these effects lasted up to 12 hours.
Clinical Applications and Side Effects
- The study also included a review of medical records for horses treated with Trazodone for various behavioral issues.
- Out of 18 clinical cases, Trazodone successfully altered behavioral problems to some degree in 17 cases. However, in two cases, the horses developed a tolerance to the drug after 14 or 21 days of use, leading to a diminished drug effect.
- Oversedation, muscle spasms, and temporary arrhythmias (irregular heartbeats) were identified as side effects of Trazodone in both the experimental and the clinical horse populations.
Cite This Article
APA
Davis JL, Schirmer J, Medlin E.
(2018).
Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active metabolite m-chlorophenylpiperazine in the horse.
J Vet Pharmacol Ther, 41(3), 393-401.
https://doi.org/10.1111/jvp.12477 Publication
Researcher Affiliations
- VA-MD College of Veterinary Medicine, Blacksburg, VA, USA.
- North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA.
- North Carolina State University College of Veterinary Medicine, Raleigh, NC, USA.
MeSH Terms
- Administration, Oral
- Animals
- Anti-Anxiety Agents / administration & dosage
- Anti-Anxiety Agents / pharmacokinetics
- Anti-Anxiety Agents / pharmacology
- Area Under Curve
- Cross-Over Studies
- Dose-Response Relationship, Drug
- Half-Life
- Horses / blood
- Male
- Piperazines / administration & dosage
- Piperazines / pharmacokinetics
- Piperazines / pharmacology
- Serotonin Receptor Agonists / administration & dosage
- Serotonin Receptor Agonists / pharmacokinetics
- Serotonin Receptor Agonists / pharmacology
- Trazodone / administration & dosage
- Trazodone / pharmacokinetics
- Trazodone / pharmacology
Conflict of Interest Statement
The authors have no conflict of interest to report.
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Citations
This article has been cited 2 times.- Marzok M, Kandeel M, Alkhodair K, Abdel-Raheem S, Ismail H, Farag A, Ibrahim H, El-Ashkar M, Shousha S, El-Khodery S. Evaluation of cardiac indices using M-mode echocardiography after administration of metoclopramide and ondansetron in donkeys (Equus asinus): an experimental study.. Front Vet Sci 2023;10:1189710.
- Hobbs K, Luethy D, Davis J, Mallicote M, Torcivia C, Kulp J, Stefanovski D, Futterman C, Cooper F, van Eps A. The effects of orally administered trazodone on ambulation and recumbency in healthy horses.. J Vet Intern Med 2023 Sep-Oct;37(5):1899-1906.
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