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Drug testing and analysis2016; 9(5); 713-720; doi: 10.1002/dta.2047

Pharmacokinetic and pharmacodynamics of xylazine administered to exercised thoroughbred horses.

Abstract: There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24 hours. The primary goal of the study reported here was to update the pharmacokinetics of xylazine following intravenous (IV) administration in order to assess the applicability of current regulatory recommendations. Pharmacodynamic parameters were determined using PK-PD modeling. Sixteen exercised adult Thoroughbred horses received a single IV dose of 200 mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96 hours and analyzed using liquid chromatography tandem mass spectrometry. Xylazine serum concentrations were best fit by a 3-compartment model. Mean ± SEM systemic clearance, volume of distribution at steady state, beta half-life and gamma half-life were 12.7 ± 0.735 mL/min/kg, 0.660 ± 0.053 L/kg, 2.79 ± 0.105 hours and 26.0 ± 1.9, respectively. Immediately following administration, horses appeared sedate as noted by a decrease in chin-to-ground distance, decreased locomotion and decreased heart rate (HR). Sedation lasted approximately 45 minutes. Glucose concentrations were elevated for 1-hour post administration. The EC50 (IC50) was 636.1, 702.2, 314.1 and 325.7 ng/mL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. The Emax (Imax) was 27.3 beats per minute, 47.5%, 42.4 cm and 0.28 mg/dL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. Pharmacokinetic parameters differ from previous reports and a prolonged detection time suggests that an extended withdrawal time, beyond current regulatory recommendations, is warranted to avoid inadvertent positive regulatory findings in performance horses. Copyright © 2016 John Wiley & Sons, Ltd.
Publication Date: 2016-09-13 PubMed ID: 27492623DOI: 10.1002/dta.2047Google Scholar: Lookup
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  • Journal Article

Summary

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The research aims to study the effects and presence of xylazine, a horse tranquilizer, in thoroughbred horses, focusing on its detection after 24 hours of administration. The results suggest that the drug exhibits a prolonged presence, thus stricter withdrawal times, beyond current regulations, are recommended to avoid unintended positive drug tests in performance horses.

Study Methodology

  • The test subjects were sixteen adult Thoroughbred horses that had undergone exercise. Each horse was administered a single intravenous dose of 200 mg of xylazine.
  • Blood and urine samples were taken at the start of the experiment and at various times for a period of up to 96 hours.
  • The samples collected were analyzed using liquid chromatography tandem mass spectrometry in order to detect xylazine concentrations.

Results and Findings

  • The analysis indicated that xylazine concentrations fit best in a 3-compartment model.
  • Key pharmacokinetic parameters such as systemic clearance, volume of distribution at steady state, and beta half-life and gamma half-life were calculated.
  • Observed effects of xylazine, post administration, included sedation (evidenced by decreased movement and heart rate) and an increase in glucose concentrations. These effects lasted for about 45 minutes and 1 hour, respectively.
  • Drug impact measurements such as EC50 (the concentration of the drug which gives half-maximal response) and Emax (maximum effect) were also noted for heart rate, atrioventicular block, chin-to-ground distance and glucose concentration.

Conclusions

  • According to the researchers, the pharmacokinetic parameters differ from previously reported data. They found a prolonged detection time for xylazine.
  • The study suggested that an extended withdrawal time, exceeding current regulatory recommendations, is necessary to avoid unintentional positive drug tests related to performance horses.

This research works towards ensuring fair practices in horse racing or horse performance events, providing comprehensive data on xylazine, and asking for revisions to be made in existing regulations. It emphasizes the prolonged presence of the drug in the horse’s system, which could lead to inadvertent positives in drug tests.

Cite This Article

APA
Knych HK, Stanley SD, McKemie DS, Arthur RM, Kass PH. (2016). Pharmacokinetic and pharmacodynamics of xylazine administered to exercised thoroughbred horses. Drug Test Anal, 9(5), 713-720. https://doi.org/10.1002/dta.2047

Publication

ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 9
Issue: 5
Pages: 713-720

Researcher Affiliations

Knych, Heather K
  • K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Stanley, Scott D
  • K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
McKemie, Daniel S
  • K.L. Maddy Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Arthur, Rick M
  • School of Veterinary Medicine, University of California, Davis, 1 Garrod Drive, Davis, CA, USA.
Kass, Phil H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA.

MeSH Terms

  • Adrenergic alpha-2 Receptor Agonists / blood
  • Adrenergic alpha-2 Receptor Agonists / pharmacology
  • Adrenergic alpha-2 Receptor Agonists / urine
  • Animals
  • Area Under Curve
  • Blood Glucose / metabolism
  • Drug Monitoring
  • Female
  • Heart Rate / drug effects
  • Horses / blood
  • Horses / physiology
  • Horses / urine
  • Locomotion / drug effects
  • Male
  • Models, Biological
  • Physical Conditioning, Animal
  • Veterinary Drugs / blood
  • Veterinary Drugs / pharmacology
  • Veterinary Drugs / urine
  • Xylazine / blood
  • Xylazine / pharmacology
  • Xylazine / urine

Citations

This article has been cited 2 times.
  1. Uney K, Yuksel M, Durna Corum D, Coskun D, Turk E, Dingil HB, Corum O. Effect of Xylazine on Pharmacokinetics and Physiological Efficacy of Intravenous Carprofen in Castrated Goats Kids.. Animals (Basel) 2023 Aug 24;13(17).
    doi: 10.3390/ani13172700pubmed: 37684964google scholar: lookup
  2. Wiederkehr A, Barbarossa A, Ringer SK, Jörger FB, Bryner M, Bettschart-Wolfensberger R. Clinical Randomized Comparison of Medetomidine and Xylazine for Isoflurane Balanced Anesthesia in Horses.. Front Vet Sci 2021;8:603695.
    doi: 10.3389/fvets.2021.603695pubmed: 33959647google scholar: lookup