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Home / Equine Research Bank / Equine Vet J / Medication control of flunixin in racing horses: Possible de...
Equine veterinary journal2021; 54(5); 979-988; doi: 10.1111/evj.13532

Medication control of flunixin in racing horses: Possible detection times using Monte Carlo simulations.

Abstract: For medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine-treated horses. Objective: To analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation. Methods: Experimental study. Methods: Drug plasma and urine concentrations following single intravenous administration of flunixin 1.1 mg/kg bodyweight (BW) in 10 horses and multiple administration of q 24 hours for 5 days in 10 horses were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data were modelled using a nonlinear mixed effect model followed by Monte Carlo simulation. Irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were calculated using the Toutain approach. Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the international screening limit (ISL) proposed by the International Federation of Horseracing Authorities (plasma: 1 ng/mL, urine; 100 ng/mL). Results: For a regimen of 1.1 mg/kg BW q 24 hours, the IPC and IUC values were 2.0 and 73.0 ng/mL respectively. Detection times in plasma above the ISL for 90% of simulated horses were estimated as 74 hours after a single 1.1 mg/kg dose administration, 149 and 199 hours after multiple doses over 5 days at either 24- or 12-hour intervals respectively. Corresponding detection times in urine were 46, 68 and 104 hours respectively. Conclusions: Only female horses were investigated. Conclusions: Statistical detection times for different flunixin meglumine regimens indicated a delay of detection time in plasma after multiple administrations under ISL.
© 2021 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2021-11-25 PubMed ID: 34719043PubMed Central: PMC9546317DOI: 10.1111/evj.13532Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research is about analyzing the duration flunixin meglumine, a medication, can be detected in race horses after administration and whether its detection can be prolonged after multiple administrations, using statistical methods and modeling techniques like Monte Carlo simulations.

Objective and Methodology

  • The research aims to investigate the pharmacokinetics of flunixin in horses and statistically analyze its detection time. This can then be used to accurately estimate withdrawal times for medication control purposes.
  • Monte Carlo simulations were used to generate a dataset for analyzing the detection period of the drug.
  • The study involved a single intravenous medication dosage of flunixin provided to 10 horses as well as multiple administrations over a 5-day period to another group of 10 horses. The plasma and urine concentration levels of the drug were observed and measured using Liquid Chromatography with tandem mass spectrometry (LC-MS/MS).
  • A non-linear mixed effect model was then used to model the data collected, followed by a Monte Carlo simulation to predict the detection times.

Results

  • The Ingenuous Plasma Concentration (IPC) and the Irrelevant Urine Concentration (IUC) were calculated using the Toutain approach. For a dosage regime of 1.1mg/kg every 24 hours, the IPC and IUC values were found to be 2.0 and 73.0 ng/mL respectively.
  • Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the international screening limit (ISL) proposed by the International Federation of Horseracing Authorities. The ISL for plasma and urine was set as 1 ng/mL and 100 ng/mL respectively.
  • The detection time was estimated to be 74 hours in plasma after a single dosage in 90% of the simulated horses. For multiple dosage over 5 days at either 24-hour or 12-hour intervals, the detection times were found to be 149 hours and 199 hours respectively.
  • Matching detection times in urine were 46 hours, 68 hours, and 104 hours respectively.

Conclusion

  • The study only investigated female horses.
  • The statistical analysis indicates a delay of the detection time in a horse’s plasma after multiple flunixin meglumine administrations under ISL conditions.

The outcomes from this research can help racehorse regulators to stipulate more scientifically based and accurate withholding times post-medication administration for racehorses.

Cite This Article

APA
Kuroda T, Minamijima Y, Nomura M, Yamashita S, Yamada M, Nagata S, Mita H, Tamura N, Fukuda K, Kuwano A, Kusano K, Toutain PL, Sato F. (2021). Medication control of flunixin in racing horses: Possible detection times using Monte Carlo simulations. Equine Vet J, 54(5), 979-988. https://doi.org/10.1111/evj.13532

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 54
Issue: 5
Pages: 979-988

Researcher Affiliations

Kuroda, Taisuke
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Minamijima, Yohei
  • Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
Nomura, Motoi
  • Equine Department Main office, Japan Racing Association, Minato-ku, Japan.
Yamashita, Shozo
  • Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
Yamada, Masayuki
  • Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
Nagata, Shunichi
  • Drug Analysis Department, Laboratory of Racing Chemistry, Utsunomiya, Japan.
Mita, Hiroshi
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Tamura, Norihisa
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Fukuda, Kentaro
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Kuwano, Atsutoshi
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.
Kusano, Kanichi
  • Equine Department Main office, Japan Racing Association, Minato-ku, Japan.
Toutain, Pierre-Louis
  • Comparative Biomedical Sciences, The Royal Veterinary College, London, UK.
  • Intheres, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
Sato, Fumio
  • Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, Shimotsuke, Japan.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Chromatography, Liquid / methods
  • Chromatography, Liquid / veterinary
  • Clonixin / analogs & derivatives
  • Female
  • Horses
  • Monte Carlo Method
  • Tandem Mass Spectrometry / veterinary

Grant Funding

  • Japan Racing Association

Conflict of Interest Statement

No competing interests have been declared.

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