Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.
Abstract: OBJECTIVE To measure concentrations of trazodone and its major metabolite in plasma and urine after administration to healthy horses and concurrently assess selected physiologic and behavioral effects of the drug. ANIMALS 11 Thoroughbred horses enrolled in a fitness training program. PROCEDURES In a pilot investigation, 4 horses received trazodone IV (n = 2) or orally (2) to select a dose for the full study; 1 horse received a vehicle control treatment IV. For the full study, trazodone was initially administered IV (1.5 mg/kg) to 6 horses and subsequently given orally (4 mg/kg), with a 5-week washout period between treatments. Blood and urine samples were collected prior to drug administration and at multiple time points up to 48 hours afterward. Samples were analyzed for trazodone and metabolite concentrations, and pharmacokinetic parameters were determined; plasma drug concentrations following IV administration best fit a 3-compartment model. Behavioral and physiologic effects were assessed. RESULTS After IV administration, total clearance of trazodone was 6.85 ± 2.80 mL/min/kg, volume of distribution at steady state was 1.06 ± 0.07 L/kg, and elimination half-life was 8.58 ± 1.88 hours. Terminal phase half-life was 7.11 ± 1.70 hours after oral administration. Horses had signs of aggression and excitation, tremors, and ataxia at the highest IV dose (2 mg/kg) in the pilot investigation. After IV drug administration in the full study (1.5 mg/kg), horses were ataxic and had tremors; sedation was evident after oral administration. CONCLUSIONS AND CLINICAL RELEVANCE Administration of trazodone to horses elicited a wide range of effects. Additional study is warranted before clinical use of trazodone in horses can be recommended.
Publication Date: 2017-09-26 PubMed ID: 28945130DOI: 10.2460/ajvr.78.10.1182Google Scholar: Lookup
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- Clinical Trial
- Journal Article
Summary
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The research study investigated the effects of trazodone, a drug, in racehorses undergoing fitness training. The drug’s traces in plasma and urine were measured, and its effect on the horses’ behavior and physiology was observed.
Research Study Procedures
- The study was initiated as a pilot investigation involving four horses. Two horses were administered trazodone intravenously (IV), and two were given the same orally. This was done to determine the suitable dose for the full study. Another horse was given a controlled IV treatment.
- In the comprehensive study, 6 horses were first given trazodone IV in the dose of 1.5 mg/kg, later followed by an oral dosage of 4mg/kg. There was a five-week gap between the two treatments.
- Blood and urine samples were taken before administering the medicine and at different time intervals in the next 48 hours. These samples were analyzed to measure the concentrations of trazodone and its metabolites.
- The pharmacokinetic properties of the drug, including the rate of absorption and expulsion from the body, were determined from these measurements.
Results
- The total clearance rate of trazodone when administered intravenously was 6.85 ± 2.80 mL/min/kg, displaying that the drug was expelled from the horse’s blood at this rate.
- The drug’s half-life or the time taken for the concentration of the drug to reduce by half was 8.58 ± 1.88 hours for IV administration and 7.11 ± 1.70 hours for oral administration.
- The performance of horses during the pilot investigation, when administered the highest IV dose (2 mg/kg), showed signs of aggression, excitation, trembling, and unsteady movement or ataxia.
- Similarly, after the IV drug administration during the full study (1.5 mg/kg), the horses showed signs of ataxia and tremors followed by evident sedation after oral administration.
Conclusions and Clinical Relevance
- The introduction of trazodone in horses resulted in a wide range of responses.
- Comprehensive study is further required before the drug can be routinely used clinically in horses due to the mixed results observed in this study.
Cite This Article
APA
Knych HK, Mama KR, Steffey EP, Stanley SD, Kass PH.
(2017).
Pharmacokinetics and selected pharmacodynamics of trazodone following intravenous and oral administration to horses undergoing fitness training.
Am J Vet Res, 78(10), 1182-1192.
https://doi.org/10.2460/ajvr.78.10.1182 Publication
Researcher Affiliations
MeSH Terms
- Administration, Intravenous
- Administration, Oral
- Animals
- Biological Availability
- Cross-Over Studies
- Female
- Half-Life
- Horses / metabolism
- Male
- Physical Conditioning, Animal
- Trazodone / administration & dosage
- Trazodone / blood
- Trazodone / pharmacokinetics
- Trazodone / urine
Citations
This article has been cited 3 times.- 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.
- Davis JL, Schirmer J, Medlin E. Pharmacokinetics, pharmacodynamics and clinical use of trazodone and its active metabolite m-chlorophenylpiperazine in the horse. J Vet Pharmacol Ther 2018 Jun;41(3):393-401.
- Joseph EJ, Love L, Mayakis M, Varner K. Preanesthetic Administration of Trazodone Does Not Impact Anesthetic Recovery Scores in Horses. Animals (Basel) 2025 Oct 6;15(19).
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