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Equine veterinary journal2020; 53(1); 102-116; doi: 10.1111/evj.13260

Pharmacokinetics and anti-inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses.

Abstract: Flunixin meglumine (FM) and phenylbutazone (PBZ) are potent anti-inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti-inflammatory effects. Objective: Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators. Methods: Two-way randomised balanced crossover experiment. Methods: Twelve Thoroughbred exercised horses received 500 mg FM IV alone or in combination with 2 g of IV PBZ 24 hours later. Blood and urine samples were collected prior to and for up to 120 hours post-drug administration. Whole blood samples were collected at various times and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of FM, PBZ and eicosanoids were measured using LC-MS/MS and noncompartmental pharmacokinetic analysis performed on concentration data. Results: Flunixin meglumine clearance was significantly increased when horses received PBZ 24 hours post-administration (P = .03). No other differences in pharmacokinetic parameters were noted between groups. Thromboxane B2 was significantly suppressed, relative to baseline for 96 hours post-FM administration. Subsequent administration of PBZ prolonged the suppression. Prostaglandin E2 was decreased for 24 hours following administration of FM with subsequent administration of PBZ prolonging the suppression until 120 hours. PGF2alpha concentrations were decreased for up to 168 hours post-FM administration. FM administration significantly decreased 15-HETE. Conclusions: Small sample size and lack of a phenylbutazone-only treatment group. Conclusions: Administration of PBZ post-FM administration increased FM clearance. The anti-inflammatory effects of FM appear to be prolonged when PBZ is administered 24 hours post-administration.
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Publication Date: 2020-04-17 PubMed ID: 32145701DOI: 10.1111/evj.13260Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

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 research investigates the effects and interaction of two anti-inflammatory drugs, flunixin meglumine (FM) and phenylbutazone (PBZ), in racehorses. It suggests that the administration of PBZ after FM increases FM’s clearance from the body and enhances its anti-inflammatory action.

Study Design and Methodology

  • This study was structured as a two-way randomized balanced crossover experiment conducted on twelve Thoroughbred horses that had undergone exercise. Each horse received either FM alone or in combination with PBZ administered 24 hours later.
  • Blood and urine samples were taken before and up to 120 hours after the administration of these drugs to monitor their clearance from the body.
  • The blood samples were also challenged with lipopolysaccharide or calcium ionophore to study their effect on eicosanoid synthesis. Eicosanoids are biological compounds known to take part in inflammation and immunity responses.
  • The concentrations of FM, PBZ and eicosanoids were measured using Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS), a technique used for identifying and quantifying small quantities of chemicals in samples. Noncompartmental pharmacokinetic analysis was performed to understand the distribution and elimination kinetics of the drugs.

Results

  • The clearance of FM increased significantly when horses received PBZ 24 hours after the administration of FM, indicating the potential pharmacokinetic interaction between these two drugs.
  • FM usage led to the suppression of Thromboxane B (an eicosanoid) relative to baseline for 96 hours. Furthermore, the administration of PBZ after FM administration extended this suppression period.
  • Prostaglandin E2 (another eicosanoid) levels decreased for 24 hours following administration of FM. The subsequent administration of PBZ prolonged this suppression until 120 hours.
  • Prostaglandin F (PGF) concentrations went down for up to 168 hours after administering FM.
  • Another finding was that FM administration decreased the levels of 15-HETE, an indicator of inflammation.

Conclusions

  • This study has some limitations, such as a small sample size and lack of a control group where only PBZ was administered.
  • Findings indicate that PBZ, when given post-administration of FM, increases the clearance of FM from the Thoroughbred horses’ bodies.
  • Furthermore, the results suggest that the anti-inflammatory action of FM is enhanced and prolonged when PBZ is administered 24 hours after FM.

Cite This Article

APA
Knych HK, Arthur RM, McKemie DS, Baden RW, Seminoff K, Kass PH. (2020). Pharmacokinetics and anti-inflammatory effects of flunixin meglumine as a sole agent and in combination with phenylbutazone in exercised Thoroughbred horses. Equine Vet J, 53(1), 102-116. https://doi.org/10.1111/evj.13260

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 53
Issue: 1
Pages: 102-116

Researcher Affiliations

Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Arthur, Rick M
  • School of Veterinary Medicine, University of California, Davis, CA, USA.
McKemie, Daniel S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Baden, Russell W
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Seminoff, Kelsey
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Kass, Philip H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, USA.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Chromatography, Liquid / veterinary
  • Clonixin / analogs & derivatives
  • Clonixin / pharmacokinetics
  • Horses / metabolism
  • Phenylbutazone / pharmacokinetics
  • Tandem Mass Spectrometry / veterinary

Grant Funding

  • Racing Medication and Testing Consortium
  • California Horse Racing Board

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Citations

This article has been cited 5 times.
  1. Kuroda T, Knych HK, Noble GK, Minamijima Y, Leung GN, Nomura M, Mizobe F, Ishikawa Y, Kusano K, Toutain PL. A Meta-Analysis of International Flunixin Pharmacokinetics in Horses: Toward Regulatory Harmonization and Individualized Detection Times Using Bayesian Paradigm. Drug Test Anal 2026 Jan;18(1):32-50.
    doi: 10.1002/dta.3961pubmed: 41137541google scholar: lookup
  2. Duggan MJS, Kearney C, Baltrimaite M, Labberté MC, Gibney R, Brama PAJ. Refinement of the Lipopolysaccharide-Induced Synovitis Model in Equine Middle Carpal Joints. Animals (Basel) 2025 Aug 22;15(17).
    doi: 10.3390/ani15172474pubmed: 40941269google scholar: lookup
  3. 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
  4. 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
  5. Waller P, Lomnicka I, Lucas C, Johnson S, Dirikolu L. The medication violations in racehorses at Louisiana racetracks from 2016 to 2020. Vet Med Sci 2022 Mar;8(2):553-560.
    doi: 10.1002/vms3.724pubmed: 34989156google scholar: lookup
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