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American journal of veterinary research2015; 76(3); 208-215; doi: 10.2460/ajvr.76.3.208

Effect of flunixin meglumine and firocoxib on ex vivo cyclooxygenase activity in horses undergoing elective surgery.

Abstract: To evaluate ex vivo cyclooxygenase (COX) inhibition and compare in vitro and ex vivo COX-1 inhibition by flunixin meglumine and firocoxib in horses. Methods: 4 healthy horses for in vitro experiments and 12 healthy horses (6 males and 6 females; 5 Thoroughbreds, 5 Warmbloods, and 2 ponies) undergoing elective surgery for ex vivo experiments. Methods: 12 horses received flunixin meglumine (1.1 mg/kg, IV, q 12 h) or firocoxib (0.09 mg/kg, IV, q 24 h). Blood samples were collected before (baseline) and 2 and 24 hours after NSAID administration. Prostanoids (thromboxane B2, prostaglandin E2, and prostaglandin E metabolites) served as indicators of COX activity, and serum drug concentrations were measured by use of high-performance liquid chromatography. An in vitro coagulation-induced thromboxane B2 assay was used to calculate drug concentration-COX-1 inhibition curves. Effect of time and treatment on COX activity was determined. Agreement between in vitro and ex vivo measurement of COX activity was assessed with Bland-Altman analysis. Results: At 2 and 24 hours after NSAID administration, COX-1 activity was reduced, compared with baseline activity, for the flunixin meglumine group only and relative COX-1 activity was significantly greater for the firocoxib group, compared with that for the flunixin meglumine group. There was no significant change in COX-2 activity after surgery for either group. Bland-Altman analysis revealed poor agreement between in vitro and ex vivo measurement of COX-1 activity. Conclusions: Compared with flunixin meglumine, firocoxib had COX-1-sparing effects ex vivo in equine patients that underwent elective surgery.
Publication Date: 2015-02-25 PubMed ID: 25710756DOI: 10.2460/ajvr.76.3.208Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This research focuses on comparing the effects of two drugs, flunixin meglumine and firocoxib, on cyclooxygenase (COX) activity in horses undergoing elective surgery, both in vitro and ex vivo. The study found that flunixin meglumine significantly reduced COX-1 activity, while firocoxib had COX-1-sparing effects.

Objective and methodology of the research

  • The purpose of the study was to compare the effects of two nonsteroidal anti-inflammatory drugs (NSAIDs), flunixin meglumine and firocoxib, on the inhibition of cyclooxygenase (COX), an enzyme that plays a crucial role in inflammation. This was carried out both in vitro (outside a living organism) and ex vivo (in or on tissue from an organism, in an external environment).
  • The experiment involved 12 healthy horses undergoing elective surgery that were divided into two groups. One group received flunixin meglumine and the other firocoxib. Four additional horses were used for in vitro experiments.
  • COX activity was measured by analyzing indicators like thromboxane B2, prostaglandin E2, and prostaglandin E metabolites. Serum drug concentrations were measured using high-performance liquid chromatography, and an in vitro coagulation-induced thromboxane B2 assay was used to calculate drug concentration and COX-1 inhibition curves.

Findings of the research

  • In the flunixin meglumine group, COX-1 activity was significantly reduced at 2 and 24 hours after NSAID administration compared to baseline activity.
  • In contrast, in the firocoxib group, COX-1 activity was significantly greater than the flunixin meglumine group. This indicates firocoxib had a sparing effect on COX-1 ex vivo.
  • The research did not find any significant change in COX-2 activity after surgery in either group.
  • Bland-Altman analysis, which assesses agreement between two measurements, revealed poor agreement between in vitro and ex vivo measurement of COX-1 activity.

Conclusions of the research

  • The research concludes that firocoxib has a sparing effect on COX-1 when compared with flunixin meglumine in horses that underwent elective surgery.
  • The study also showed a poor correlation between in vitro and ex vivo measurements, indicating potential discrepancies between laboratory and real-life conditions.

Cite This Article

APA
Duz M, Parkin TD, Cullander RM, Marshall JF. (2015). Effect of flunixin meglumine and firocoxib on ex vivo cyclooxygenase activity in horses undergoing elective surgery. Am J Vet Res, 76(3), 208-215. https://doi.org/10.2460/ajvr.76.3.208

Publication

ISSN: 1943-5681
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 76
Issue: 3
Pages: 208-215

Researcher Affiliations

Duz, Marco
  • Boyd Orr Centre for Population and Ecosystem Health, School of Veterinary Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G61 1QH, Scotland.
Parkin, Tim D
    Cullander, Rose M
      Marshall, John F

        MeSH Terms

        • 4-Butyrolactone / administration & dosage
        • 4-Butyrolactone / analogs & derivatives
        • 4-Butyrolactone / pharmacology
        • Animals
        • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
        • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
        • Clonixin / administration & dosage
        • Clonixin / analogs & derivatives
        • Clonixin / pharmacology
        • Cyclooxygenase 1 / drug effects
        • Cyclooxygenase 2 / drug effects
        • Elective Surgical Procedures / veterinary
        • Female
        • Horses / blood
        • Horses / surgery
        • Male
        • Sulfones / administration & dosage
        • Sulfones / pharmacology

        Citations

        This article has been cited 5 times.
        1. Shapiro AJ, Kimble B, Hulst F, Herrin KV, Marschner C, Chen CJ, Govendir M. Pharmacokinetic profile of oral firocoxib in the koala (Phascolarctos cinereus). PLoS One 2025;20(9):e0332448.
          doi: 10.1371/journal.pone.0332448pubmed: 41026701google scholar: lookup
        2. Laves J, Wergin M, Bauer N, Müller SF, Failing K, Büttner K, Hagen A, Melzer M, Röcken M. The effect of Traumeel LT ad us. vet. on the perioperative inflammatory response after castration of stallions: a prospective, randomized, double-blinded study. Front Vet Sci 2024;11:1342345.
          doi: 10.3389/fvets.2024.1342345pubmed: 39415958google scholar: lookup
        3. Fadel C, Giorgi M. Synopsis of the pharmacokinetics, pharmacodynamics, applications, and safety of firocoxib in horses. Vet Anim Sci 2023 Mar;19:100286.
          doi: 10.1016/j.vas.2023.100286pubmed: 36684818google scholar: lookup
        4. Donnell JR, Frisbie DD. Use of firocoxib for the treatment of equine osteoarthritis. Vet Med (Auckl) 2014;5:159-168.
          doi: 10.2147/VMRR.S70207pubmed: 32670856google scholar: lookup
        5. Ziegler A, Fogle C, Blikslager A. Update on the use of cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs in horses. J Am Vet Med Assoc 2017 Jun 1;250(11):1271-1274.
          doi: 10.2460/javma.250.11.1271pubmed: 28509650google scholar: lookup