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Journal of veterinary pharmacology and therapeutics2021; 44(5); 745-753; doi: 10.1111/jvp.12993

Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses.

Abstract: Flunixin meglumine is a highly efficacious nonsteroidal anti-inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500 mg and blood and urine samples collected for up to 96 h post-administration. Serum for determination of thromboxane concentrations and whole blood samples was collected at various time and challenged with lipopolysaccharide, calcium ionophore, or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flunixin, 5-OH flunixin, and eicosanoids were measured using LC-MS/MS and non-compartmental pharmacokinetic analysis performed on concentration data. Serum concentrations of flunixin and 5-OH flunixin were above the limit of quantitation at 96 h post-administration in both serum and urine. The mean (range) for Cmax , Tmax and the terminal half-life were 515.6 (369.7-714.0) ng/ml, 8.67 (8.0 12.0) h, and 22.4 (18.3-42.5) h, respectively. Following transdermal administration, based on effects on eicosanoid synthesis, flunixin meglumine inhibited cyclooxygenase 1 and 2 and 15-lipooxygenase activity, with anti-inflammatory effects lasting for 24-72 h.
© 2021 John Wiley & Sons Ltd.
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Publication Date: 2021-06-25 PubMed ID: 34173263DOI: 10.1111/jvp.12993Google 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.

This study evaluated the effects of the transdermal application of flunixin meglumine, a nonsteroidal anti-inflammatory drug, on horses and its influence on inflammatory markers. The researchers found this drug effectively suppressed inflammation for a period of 24 to 72 hours.

Methodology

  • Six horses were involved in this investigation. They were given a one-time transdermal dosage of 500 mg of flunixin meglumine.
  • For up to 96 hours following administration, urine and blood samples were gathered. These samples were then tested to observe the action of flunixin meglumine in the body.
  • An ex-vivo test, which simulates the conditions found inside the body, was conducted using whole blood samples. The samples were stimulated to synthesize eicosanoids, a type of fat known to have inflammatory and anti-inflammatory effects.
  • The researchers then used a technique known as liquid chromatography tandem mass spectrometry (LC-MS/MS) to quantify the concentrations of flunixin meglumine, its metabolite (5-OH flunixin), and the synthesized eicosanoids in the samples.

Results

  • At 96 hours post-administration, serum and urine samples showed quantifiable amounts of flunixin and 5-OH flunixin. This shows that flunixin and its metabolite continue to linger in the body of horses significantly long after the drug is administered.
  • The results from the ex vivo test showed that flunixin meglumine significantly inhibited the activity of three different enzymes involved in the inflammatory response: cyclooxygenase 1 and 2, and 15-lipooxygenase. This points to the wide-ranging anti-inflammatory effects of flunixin meglumine in horses.
  • The researchers found that the anti-inflammatory effect of the drug lasted from 24 to 72 hours, showing its continued efficacy over a substantial span of time.
  • Overall, the findings suggest that flunixin meglumine could be an effective drug for managing inflammation in horses, given its long-lasting and wide-ranging anti-inflammatory effects, as revealed by its continued presence in the body and its inhibition of various enzymes linked to inflammation.

Cite This Article

APA
Knych HK, Arthur RM, Gretler SR, McKemie DS, Goldin S, Kass PH. (2021). Pharmacokinetics of transdermal flunixin meglumine and effects on biomarkers of inflammation in horses. J Vet Pharmacol Ther, 44(5), 745-753. https://doi.org/10.1111/jvp.12993

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 44
Issue: 5
Pages: 745-753

Researcher Affiliations

Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
Arthur, Rick M
  • School of Veterinary Medicine, University of California, Davis, California, USA.
Gretler, Sophie R
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
McKemie, Daniel S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
Goldin, Skyler
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
Kass, Philip H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.

MeSH Terms

  • Administration, Cutaneous
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Biomarkers
  • Cattle
  • Chromatography, Liquid / veterinary
  • Clonixin / analogs & derivatives
  • Clonixin / pharmacokinetics
  • Horse Diseases / drug therapy
  • Horses
  • Inflammation / veterinary
  • Tandem Mass Spectrometry / veterinary

Grant Funding

  • California Horse Racing Board
  • Racing Medication and Testing Consortium

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Citations

This article has been cited 3 times.
  1. McLean AK, Falt T, Abdelfattah EM, Middlebrooks B, Gretler S, Spier S, Turoff D, Navas Gonzalez FJ, Knych HK. Transdermal Flunixin Meglumine as a Pain Relief in Donkeys: A Pharmacokinetics Pilot Study. Metabolites 2023 Jun 21;13(7).
    doi: 10.3390/metabo13070776pubmed: 37512483google scholar: lookup
  2. Mercer MA, Davis JL, McKenzie HC. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses. Animals (Basel) 2023 May 10;13(10).
    doi: 10.3390/ani13101597pubmed: 37238029google scholar: lookup
  3. Ravuri HG, Satake N, Balmanno A, Skinner J, Kempster S, Mills PC. Pharmacokinetic Evaluation of a Novel Transdermal Ketoprofen Formulation in Healthy Dogs. Pharmaceutics 2022 Mar 15;14(3).
    doi: 10.3390/pharmaceutics14030646pubmed: 35336020google scholar: lookup
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