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Equine veterinary journal2009; 41(5); 419-422; doi: 10.2746/042516409x382079

Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise.

Abstract: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. Objective: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. Methods: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. Results: Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. Conclusions: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.
Publication Date: 2009-08-01 PubMed ID: 19642399DOI: 10.2746/042516409x382079Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research examines the impact of exercise on how the drug detomidine, used for sedation, is processed in Thoroughbred horses. The findings suggested that after intense exercise, the drug is distributed more widely in the horse’s body, resulting in a slower rate of elimination and lower peak concentrations in the blood.

Objective and Methods

  • The objective of the study was to understand whether the pharmacokinetics, or how the body processes a drug, of detomidine is different when administered to horses during recovery from intense exercise compared to when at rest.
  • Six Thoroughbred horses were first conditioned with exercise on a treadmill, running a simulated race at a speed resulting in 120% of their maximum oxygen consumption.
  • One minute after the end of the exercise, each horse was given detomidine. This process was repeated with the same dose of the drug given to the same horses at least 14 days later while the horses were standing idle.

Sample Collection and Analysis

  • Blood samples with added heparin were collected at various time intervals during both trials.
  • The concentration of detomidine in the plasma was then measured using liquid chromatography-mass spectrometry, a laboratory process used for identifying and quantifying components in a sample.
  • The gathered plasma concentration versus time data was analysed with nonlinear regression analysis, a statistical method used to model the relationship between a dependent variable and one or more independent variables.

Results

  • The research revealed that after exercise, the initial plasma concentration of the drug was significantly lower, while the time for the drug to reach half its original concentration and the average residence time of the drug in the body were both significantly longer.
  • The distribution volume of the drug was higher post exercise, although there was no significant difference in how fast the drug was cleared from the plasma between the two treatments.

Conclusions

  • The study concluded that detomidine, when administered intravenously immediately after exercise, is more widely distributed throughout the body compared to when given at rest. This results in lower peak plasma concentrations and a slower rate of elimination.
  • The implication of these findings is that a higher dose of detomidine may be needed to achieve the same effect in horses post-exercise as compared to at rest. Furthermore, subsequent doses needed to maintain the effect may be less frequent due to the drug’s slower elimination.

Cite This Article

APA
Hubbell JA, Sams RA, Schmall LM, Robertson JT, Hinchcliff KW, Muir WW. (2009). Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise. Equine Vet J, 41(5), 419-422. https://doi.org/10.2746/042516409x382079

Publication

ISSN: 0425-1644
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 41
Issue: 5
Pages: 419-422

Researcher Affiliations

Hubbell, J A E
  • Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Sams, R A
    Schmall, L M
      Robertson, J T
        Hinchcliff, K W
          Muir, W W

            MeSH Terms

            • Analgesics / blood
            • Analgesics / pharmacokinetics
            • Animals
            • Female
            • Half-Life
            • Horses / metabolism
            • Imidazoles / blood
            • Imidazoles / pharmacokinetics
            • Male
            • Physical Conditioning, Animal / physiology

            Citations

            This article has been cited 2 times.
            1. Bischoff K, Jaeger R, Ebel JG. An unusual case of relay pentobarbital toxicosis in a dog. J Med Toxicol 2011 Sep;7(3):236-9.
              doi: 10.1007/s13181-011-0160-8pubmed: 21660622google scholar: lookup
            2. Knych HK. Administration Studies in Equine Antidoping Research: Designing Scientific Investigations to Effectively Direct Medication Control in Racehorses. Drug Test Anal 2025 Sep;17(9):1560-1566.
              doi: 10.1002/dta.3857pubmed: 39876751google scholar: lookup