Pharmacokinetic and pharmacodynamics of xylazine administered to exercised thoroughbred horses

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7 Citations (Scopus)

Abstract

There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24hours. 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 200mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96hours 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±0.735mL/min/kg, 0.660±0.053L/kg, 2.79±0.105hours 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 45minutes. Glucose concentrations were elevated for 1-hour post administration. The EC50 (IC50) was 636.1, 702.2, 314.1 and 325.7ng/mL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. The Emax (Imax) was 27.3 beats per minute, 47.5%, 42.4cm and 0.28mg/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.

Original languageEnglish (US)
JournalDrug Testing and Analysis
DOIs
StateAccepted/In press - 2016

Fingerprint

Pharmacodynamics
Xylazine
Pharmacokinetics
horse
Chin
Horses
glucose
Atrioventricular Block
Heart Rate
Glucose
half life
Half-Life
serum
Liquid chromatography
locomotion
Locomotion
Tandem Mass Spectrometry
Serum
Liquid Chromatography
Intravenous Administration

Keywords

  • Alpha2 adrenergic agonist
  • Drug doping
  • Horse
  • Pharmacodynamics
  • Pharmacokinetics
  • Racehorse, xylazine

ASJC Scopus subject areas

  • Analytical Chemistry
  • Environmental Chemistry
  • Pharmaceutical Science
  • Spectroscopy

Cite this

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title = "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 24hours. 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 200mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96hours 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±0.735mL/min/kg, 0.660±0.053L/kg, 2.79±0.105hours 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 45minutes. Glucose concentrations were elevated for 1-hour post administration. The EC50 (IC50) was 636.1, 702.2, 314.1 and 325.7ng/mL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. The Emax (Imax) was 27.3 beats per minute, 47.5{\%}, 42.4cm and 0.28mg/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.",
keywords = "Alpha2 adrenergic agonist, Drug doping, Horse, Pharmacodynamics, Pharmacokinetics, Racehorse, xylazine",
author = "Knych, {Heather K} and Stanley, {Scott D} and Mckemie, {Daniel S.} and Rick Arthur and Kass, {Philip H}",
year = "2016",
doi = "10.1002/dta.2047",
language = "English (US)",
journal = "Drug Testing and Analysis",
issn = "1942-7603",
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TY - JOUR

T1 - Pharmacokinetic and pharmacodynamics of xylazine administered to exercised thoroughbred horses

AU - Knych, Heather K

AU - Stanley, Scott D

AU - Mckemie, Daniel S.

AU - Arthur, Rick

AU - Kass, Philip H

PY - 2016

Y1 - 2016

N2 - There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24hours. 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 200mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96hours 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±0.735mL/min/kg, 0.660±0.053L/kg, 2.79±0.105hours 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 45minutes. Glucose concentrations were elevated for 1-hour post administration. The EC50 (IC50) was 636.1, 702.2, 314.1 and 325.7ng/mL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. The Emax (Imax) was 27.3 beats per minute, 47.5%, 42.4cm and 0.28mg/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.

AB - There is limited data describing xylazine serum concentrations in the horse and no reports of concentrations beyond 24hours. 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 200mg of xylazine. Blood and urine samples were collected at time 0 and at various times for up to 96hours 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±0.735mL/min/kg, 0.660±0.053L/kg, 2.79±0.105hours 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 45minutes. Glucose concentrations were elevated for 1-hour post administration. The EC50 (IC50) was 636.1, 702.2, 314.1 and 325.7ng/mL for HR, atrioventricular block, chin-to-ground distance and glucose concentrations, respectively. The Emax (Imax) was 27.3 beats per minute, 47.5%, 42.4cm and 0.28mg/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.

KW - Alpha2 adrenergic agonist

KW - Drug doping

KW - Horse

KW - Pharmacodynamics

KW - Pharmacokinetics

KW - Racehorse, xylazine

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U2 - 10.1002/dta.2047

DO - 10.1002/dta.2047

M3 - Article

C2 - 27492623

AN - SCOPUS:84987625536

JO - Drug Testing and Analysis

JF - Drug Testing and Analysis

SN - 1942-7603

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