Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse

Heather K Knych, C. R. Corado, D. S. Mckemie, Eugene Steffey

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Reasons for performing study: Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species. Objectives: To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse. Methods: Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72h post administration. Plasma samples were analysed using liquid chromatography-mass spectrometry and data analysed using noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were also assessed. Results: Maximal measured plasma tramadol concentrations were 454 ± 101.6, 1086.7 ± 330.7 and 1697.9 ± 406.1ng/ml for 0.5, 1.5 and 3mg/kg bwt, respectively. Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24.6 to 25.0ml/min/kg, 2.66 to 3.33l/kg and 2.17 to 3.05h, respectively. Following administration of 0.5, 1.5 and 3mg/kg bwt tramadol, the maximal measured plasma concentrations of the active metabolite, O-desmethyltramadol, were 3.9 ± 1.9, 9.6 ± 4.8 and 12.9 ± 5.2ng/ml, respectively. Muscle fasiculations and tremors were seen following administration of the 2 high doses. No significant changes in chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were observed. Conclusions and potential relevance: This study confirms and extends previous studies describing the pharmacokinetics of tramadol following i.v. administration to the horse. Plasma tramadol concentrations exceeded those necessary for analgesia in human patients; however, further studies are necessary to determine plasma concentrations of tramadol necessary for analgesic efficacy in the horse. These results support further investigation of the analgesic efficacy of tramadol in the horse.

Original languageEnglish (US)
Pages (from-to)490-496
Number of pages7
JournalEquine Veterinary Journal
Volume45
Issue number4
DOIs
StatePublished - Jul 2013

Fingerprint

Tramadol
pharmacology
intravenous injection
Intravenous Administration
pharmacokinetics
Horses
Pharmacokinetics
horses
analgesics
heart rate
dosage
Analgesics
metabolites
Chin
analgesic effect
administered dose
analgesia
liquid chromatography
half life
Heart Rate

Keywords

  • Analgesia
  • Horse
  • Pharmacodynamics
  • Pharmacokinetics
  • Tramdol

ASJC Scopus subject areas

  • Equine

Cite this

Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse. / Knych, Heather K; Corado, C. R.; Mckemie, D. S.; Steffey, Eugene.

In: Equine Veterinary Journal, Vol. 45, No. 4, 07.2013, p. 490-496.

Research output: Contribution to journalArticle

@article{b31e279b554e403aa06582f71b1ed805,
title = "Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse",
abstract = "Reasons for performing study: Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species. Objectives: To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse. Methods: Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72h post administration. Plasma samples were analysed using liquid chromatography-mass spectrometry and data analysed using noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were also assessed. Results: Maximal measured plasma tramadol concentrations were 454 ± 101.6, 1086.7 ± 330.7 and 1697.9 ± 406.1ng/ml for 0.5, 1.5 and 3mg/kg bwt, respectively. Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24.6 to 25.0ml/min/kg, 2.66 to 3.33l/kg and 2.17 to 3.05h, respectively. Following administration of 0.5, 1.5 and 3mg/kg bwt tramadol, the maximal measured plasma concentrations of the active metabolite, O-desmethyltramadol, were 3.9 ± 1.9, 9.6 ± 4.8 and 12.9 ± 5.2ng/ml, respectively. Muscle fasiculations and tremors were seen following administration of the 2 high doses. No significant changes in chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were observed. Conclusions and potential relevance: This study confirms and extends previous studies describing the pharmacokinetics of tramadol following i.v. administration to the horse. Plasma tramadol concentrations exceeded those necessary for analgesia in human patients; however, further studies are necessary to determine plasma concentrations of tramadol necessary for analgesic efficacy in the horse. These results support further investigation of the analgesic efficacy of tramadol in the horse.",
keywords = "Analgesia, Horse, Pharmacodynamics, Pharmacokinetics, Tramdol",
author = "Knych, {Heather K} and Corado, {C. R.} and Mckemie, {D. S.} and Eugene Steffey",
year = "2013",
month = "7",
doi = "10.1111/j.2042-3306.2012.00688.x",
language = "English (US)",
volume = "45",
pages = "490--496",
journal = "Equine veterinary journal. Supplement",
issn = "2042-3306",
publisher = "British Equine Veterinary Association",
number = "4",

}

TY - JOUR

T1 - Pharmacokinetics and selected pharmacodynamic effects of tramadol following intravenous administration to the horse

AU - Knych, Heather K

AU - Corado, C. R.

AU - Mckemie, D. S.

AU - Steffey, Eugene

PY - 2013/7

Y1 - 2013/7

N2 - Reasons for performing study: Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species. Objectives: To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse. Methods: Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72h post administration. Plasma samples were analysed using liquid chromatography-mass spectrometry and data analysed using noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were also assessed. Results: Maximal measured plasma tramadol concentrations were 454 ± 101.6, 1086.7 ± 330.7 and 1697.9 ± 406.1ng/ml for 0.5, 1.5 and 3mg/kg bwt, respectively. Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24.6 to 25.0ml/min/kg, 2.66 to 3.33l/kg and 2.17 to 3.05h, respectively. Following administration of 0.5, 1.5 and 3mg/kg bwt tramadol, the maximal measured plasma concentrations of the active metabolite, O-desmethyltramadol, were 3.9 ± 1.9, 9.6 ± 4.8 and 12.9 ± 5.2ng/ml, respectively. Muscle fasiculations and tremors were seen following administration of the 2 high doses. No significant changes in chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were observed. Conclusions and potential relevance: This study confirms and extends previous studies describing the pharmacokinetics of tramadol following i.v. administration to the horse. Plasma tramadol concentrations exceeded those necessary for analgesia in human patients; however, further studies are necessary to determine plasma concentrations of tramadol necessary for analgesic efficacy in the horse. These results support further investigation of the analgesic efficacy of tramadol in the horse.

AB - Reasons for performing study: Both the potential analgesic effect and the conflicting reports describing tramadol disposition in the horse warrant further study of the pharmacokinetics of tramadol in this species. Objectives: To describe the pharmacokinetics of tramadol and its metabolites, O-desmethyltramadol and N-desmethyltramadol, following i.v. administration of 3 doses to the horse. Methods: Nine adult horses received a single i.v. dose of 0.5, 1.5 and 3mg/kg bwt tramadol. Blood samples were collected prior to and at various times up to 72h post administration. Plasma samples were analysed using liquid chromatography-mass spectrometry and data analysed using noncompartmental analysis. Chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were also assessed. Results: Maximal measured plasma tramadol concentrations were 454 ± 101.6, 1086.7 ± 330.7 and 1697.9 ± 406.1ng/ml for 0.5, 1.5 and 3mg/kg bwt, respectively. Depending on the dose administered, the tramadol clearance, volume of distribution and half-life ranged from 24.6 to 25.0ml/min/kg, 2.66 to 3.33l/kg and 2.17 to 3.05h, respectively. Following administration of 0.5, 1.5 and 3mg/kg bwt tramadol, the maximal measured plasma concentrations of the active metabolite, O-desmethyltramadol, were 3.9 ± 1.9, 9.6 ± 4.8 and 12.9 ± 5.2ng/ml, respectively. Muscle fasiculations and tremors were seen following administration of the 2 high doses. No significant changes in chin-to-ground distance, heart rate and rhythm, step count and gastrointestinal activity were observed. Conclusions and potential relevance: This study confirms and extends previous studies describing the pharmacokinetics of tramadol following i.v. administration to the horse. Plasma tramadol concentrations exceeded those necessary for analgesia in human patients; however, further studies are necessary to determine plasma concentrations of tramadol necessary for analgesic efficacy in the horse. These results support further investigation of the analgesic efficacy of tramadol in the horse.

KW - Analgesia

KW - Horse

KW - Pharmacodynamics

KW - Pharmacokinetics

KW - Tramdol

UR - http://www.scopus.com/inward/record.url?scp=84878936178&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878936178&partnerID=8YFLogxK

U2 - 10.1111/j.2042-3306.2012.00688.x

DO - 10.1111/j.2042-3306.2012.00688.x

M3 - Article

C2 - 23145962

AN - SCOPUS:84878936178

VL - 45

SP - 490

EP - 496

JO - Equine veterinary journal. Supplement

JF - Equine veterinary journal. Supplement

SN - 2042-3306

IS - 4

ER -