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Home / Equine Research Bank / Pharmacol Res / COX-1 and COX-2 inhibition in horse blood by phenylbutazone,...
Pharmacological research2005; 52(4); 302-306; doi: 10.1016/j.phrs.2005.04.004

COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis.

Abstract: We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2 selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower COX-2 selectivity than at IC50. We therefore propose that the selectivity of NSAIDs should be assessed at the 80% as well as 50% inhibition level.
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Publication Date: 2005-06-09 PubMed ID: 15939622DOI: 10.1016/j.phrs.2005.04.004Google Scholar: Lookup
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  • Comparative Study
  • Journal Article

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 paper examines the inhibitory effects of four different non-steroidal anti-inflammatory drugs (NSAIDs) on horse blood cyclooxygenases, in an in vitro setting. The study found that meloxicam and carprofen are more selective in inhibiting COX-2 than phenylbutazone and flunixin, particularly for meloxicam. However, the researchers propose assessing the selectivity of these drugs at both 50% and 80% inhibition levels.

Introduction to the Study

  • This research analyzes the inhibitory effects the non-steroidal anti-inflammatory drugs (NSAIDs) phenylbutazone, flunixin, carprofen, and meloxicam have on horse blood cyclooxygenases, COX-1 and COX-2 using in vitro studies.

Methodology

  • The researchers used enzyme-linked assays to measure and provide a quantitative comparison of the inhibitory potential of these NSAIDs.
  • IC50 and IC80, terms used in pharmacology that explain the concentration of a drug necessary for 50% and 80% inhibition in vitro, were measured for all the NSAIDs mentioned against COX-1 and COX-2.

Findings

  • The study discovered that meloxicam and carprofen were more selective inhibitors of COX-2 than phenylbutazone and flunixin.
  • Specifically, meloxicam was singled out as the most advantageous of the four tested drugs for horses.

Further Observations and Recommendations

  • At the IC80 level, phenylbutazone and flunixin demonstrated greater COX-2 selectivity with increases of +134.4% and +29.7% respectively. This is opposed to the IC50 level.
  • On the other hand, meloxicam and carprofen showed lower COX-2 selectivity at IC80 than at IC50, with drop offs of -41.2% and -12.9% respectively.
  • This led the researchers to propose that the selectivity of NSAIDs should be measured at both the 50% and 80% inhibitory levels. Doing so would give a broader and more accurate assessment of their activity and potential utility in veterinary practice.

Cite This Article

APA
Beretta C, Garavaglia G, Cavalli M. (2005). COX-1 and COX-2 inhibition in horse blood by phenylbutazone, flunixin, carprofen and meloxicam: an in vitro analysis. Pharmacol Res, 52(4), 302-306. https://doi.org/10.1016/j.phrs.2005.04.004

Publication

Pharmacological research
ISSN: 1043-6618
NlmUniqueID: 8907422
Country: Netherlands
Language: English
Volume: 52
Issue: 4
Pages: 302-306

Researcher Affiliations

Beretta, C
  • Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, Via Celoria 10, 20133 Milan, Italy. carlo.beretta@unimi.it
Garavaglia, G
    Cavalli, M

      MeSH Terms

      • Animals
      • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
      • Carbazoles / pharmacology
      • Clonixin / analogs & derivatives
      • Clonixin / pharmacology
      • Cyclooxygenase Inhibitors / pharmacology
      • Dinoprostone / blood
      • Female
      • Horses
      • In Vitro Techniques
      • Male
      • Meloxicam
      • Phenylbutazone / pharmacology
      • Thiazines / pharmacology
      • Thiazoles / pharmacology
      • Thromboxane B2 / blood

      Citations

      This article has been cited 35 times.
      1. Tsekouras N, Christodoulopoulos MAB, Meletis E, Kousoulis C, Kostoulas P, Pantazis V, Papatsiros VG, Dimoveli K, Gougoulis D. Associations Between Non-Steroidal and Steroidal Anti-Inflammatory Drug Use, Welfare, and Milk Production in Dairy Sheep: A Multivariate Study. Animals (Basel) 2025 Apr 11;15(8).
        doi: 10.3390/ani15081104pubmed: 40281937google scholar: lookup
      2. Kemp KL, Yuen NKY, Skinner JE, Bertin FR. Effect of Phenylbutazone Administration on Insulin Sensitivity in Horses With Insulin Dysregulation. J Vet Intern Med 2025 Mar-Apr;39(2):e70028.
        doi: 10.1111/jvim.70028pubmed: 40011055google scholar: lookup
      3. Kemp KL, Skinner JE, Bertin FR. Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation. J Vet Intern Med 2025 Jan-Feb;39(1):e17256.
        doi: 10.1111/jvim.17256pubmed: 39578373google scholar: lookup
      4. Kemp KL, Skinner JE, Bertin FR. Effect of phenylbutazone on insulin secretion in horses with insulin dysregulation. J Vet Intern Med 2024 Mar-Apr;38(2):1177-1184.
        doi: 10.1111/jvim.17013pubmed: 38363029google scholar: lookup
      5. Singh H, Kumar R, Mazumder A. Pyrazoline and Analogs: Substrate-based Synthetic Strategies. Curr Org Synth 2024;21(7):823-836.
        doi: 10.2174/1570179421666230822100043pubmed: 37608650google scholar: lookup
      6. 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
      7. Sarvi JY, Gardhouse SM, Kleinhenz MD, Hocker SE, Weeder MM, Montgomery SR, Rooney TA. Measurement of Cyclooxygenase Products in Plasma as Markers for Inhibition of Cyclooxygenase Isoforms by Oral Meloxicam in New Zealand White Rabbits (Oryctolagus cuniculus ). J Am Assoc Lab Anim Sci 2023 May 1;62(3):254-259.
        doi: 10.30802/AALAS-JAALAS-22-000109pubmed: 37045554google scholar: lookup
      8. Flood J, Stewart AJ. Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses. Animals (Basel) 2022 Oct 26;12(21).
        doi: 10.3390/ani12212939pubmed: 36359062google scholar: lookup
      9. Nixon E, Chittenden JT, Baynes RE, Messenger KM. Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration and tail-docking. J Vet Pharmacol Ther 2022 Sep;45(5):450-466.
        doi: 10.1111/jvp.13083pubmed: 35833463google scholar: lookup
      10. Morón-Elorza P, Cañizares-Cooz D, Rojo-Solis C, Álvaro-Álvarez T, Valls-Torres M, García-Párraga D, Encinas T. Pharmacokinetics of the Anti-Inflammatory Drug Meloxicam after Single 1.5 mg/kg Intramuscular Administration to Undulate Skates (Raja undulata). Vet Sci 2022 Apr 28;9(5).
        doi: 10.3390/vetsci9050216pubmed: 35622744google scholar: lookup
      11. Daniel C, Bhakta S. Immunobiology of tubercle bacilli and prospects of immunomodulatory drugs to tackle tuberculosis (TB) and other non-tubercular mycobacterial infections. Immunobiology 2022 May;227(3):152224.
        doi: 10.1016/j.imbio.2022.152224pubmed: 35533535google scholar: lookup
      12. Lemonnier LC, Thorin C, Meurice A, Dubus A, Touzot-Jourde G, Couroucé A, Leroux AA. Comparison of Flunixin Meglumine, Meloxicam and Ketoprofen on Mild Visceral Post-Operative Pain in Horses. Animals (Basel) 2022 Feb 21;12(4).
        doi: 10.3390/ani12040526pubmed: 35203234google scholar: lookup
      13. Mainau E, Llonch P, Temple D, Goby L, Manteca X. Alteration in Activity Patterns of Cows as a Result of Pain Due to Health Conditions. Animals (Basel) 2022 Jan 12;12(2).
        doi: 10.3390/ani12020176pubmed: 35049798google scholar: lookup
      14. Chuncharunee A, Khosuk P, Naovarat R, Kaliyadan F, Sreekanth GP. ASPP 092, a phenolic diarylheptanoid from Curcuma comosa suppresses experimentally-induced inflammatory ear edema in mice. Saudi J Biol Sci 2021 Oct;28(10):5937-5946.
        doi: 10.1016/j.sjbs.2021.06.056pubmed: 34588910google scholar: lookup
      15. Tucker L, Trumble TN, Groschen D, Dobbs E, Baldo CF, Wendt-Hornickle E, Guedes AGP. Targeting Soluble Epoxide Hydrolase and Cyclooxygenases Enhance Joint Pain Control, Stimulate Collagen Synthesis, and Protect Chondrocytes From Cytokine-Induced Apoptosis. Front Vet Sci 2021;8:685824.
        doi: 10.3389/fvets.2021.685824pubmed: 34422942google scholar: lookup
      16. Cui L, Qu Y, Cai H, Wang H, Dong J, Li J, Qian C, Li J. Meloxicam Inhibited the Proliferation of LPS-Stimulated Bovine Endometrial Epithelial Cells Through Wnt/β-Catenin and PI3K/AKT Pathways. Front Vet Sci 2021;8:637707.
        doi: 10.3389/fvets.2021.637707pubmed: 34307514google scholar: lookup
      17. Trimboli F, Ragusa M, Piras C, Lopreiato V, Britti D. Outcomes from Experimental Testing of Nonsteroidal Anti-Inflammatory Drug (NSAID) Administration during the Transition Period of Dairy Cows. Animals (Basel) 2020 Oct 8;10(10).
        doi: 10.3390/ani10101832pubmed: 33050071google scholar: lookup
      18. Kittrell HC, Mochel JP, Brown JT, Forseth AMK, Hayman KP, Rajewski SM, Coetzee JF, Schneider BK, Ratliffe B, Skoland KJ, Karriker LA. Pharmacokinetics of Intravenous, Intramuscular, Oral, and Transdermal Administration of Flunixin Meglumine in Pre-wean Piglets. Front Vet Sci 2020;7:586.
        doi: 10.3389/fvets.2020.00586pubmed: 33005646google scholar: lookup
      19. 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
      20. Czub MP, Handing KB, Venkataramany BS, Cooper DR, Shabalin IG, Minor W. Albumin-Based Transport of Nonsteroidal Anti-Inflammatory Drugs in Mammalian Blood Plasma. J Med Chem 2020 Jul 9;63(13):6847-6862.
        doi: 10.1021/acs.jmedchem.0c00225pubmed: 32469516google scholar: lookup
      21. Huang K, Masuda A, Chen G, Bushra S, Kamon M, Araki T, Kinoshita M, Ohkawara B, Ito M, Ohno K. Inhibition of cyclooxygenase-1 by nonsteroidal anti-inflammatory drugs demethylates MeR2 enhancer and promotes Mbnl1 transcription in myogenic cells. Sci Rep 2020 Feb 13;10(1):2558.
        doi: 10.1038/s41598-020-59517-ypubmed: 32054946google scholar: lookup
      22. Persson-Sjodin E, Hernlund E, Pfau T, Haubro Andersen P, Holm Forsström K, Rhodin M. Effect of meloxicam treatment on movement asymmetry in riding horses in training. PLoS One 2019;14(8):e0221117.
        doi: 10.1371/journal.pone.0221117pubmed: 31408491google scholar: lookup
      23. Mendoza FJ, Serrano-Rodriguez JM, Perez-Ecija A. Pharmacokinetics of meloxicam after oral administration of a granule formulation to healthy horses. J Vet Intern Med 2019 Mar;33(2):961-967.
        doi: 10.1111/jvim.15433pubmed: 30768821google scholar: lookup
      24. Borges RS, Palheta IC, Ota SSB, Morais RB, Barros VA, Ramos RS, Silva RC, Costa JDS, Silva CHTP, Campos JM, Santos CBR. Toward of Safer Phenylbutazone Derivatives by Exploration of Toxicity Mechanism. Molecules 2019 Jan 1;24(1).
        doi: 10.3390/molecules24010143pubmed: 30609687google scholar: lookup
      25. Whitfield-Cargile CM, Chamoun-Emanuelli AM, Cohen ND, Richardson LM, Ajami NJ, Dockery HJ. Differential effects of selective and non-selective cyclooxygenase inhibitors on fecal microbiota in adult horses. PLoS One 2018;13(8):e0202527.
        doi: 10.1371/journal.pone.0202527pubmed: 30138339google scholar: lookup
      26. Strugała P, Tronina T, Huszcza E, Gabrielska J. Bioactivity In Vitro of Quercetin Glycoside Obtained in Beauveria bassiana Culture and Its Interaction with Liposome Membranes. Molecules 2017 Sep 11;22(9).
        doi: 10.3390/molecules22091520pubmed: 28891998google scholar: lookup
      27. 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
      28. Banse H, Cribb AE. Comparative efficacy of oral meloxicam and phenylbutazone in 2 experimental pain models in the horse. Can Vet J 2017 Feb;58(2):157-167.
        pubmed: 28216685
      29. Song JS, Park SJ, Choi JY, Kim JS, Kang MH, Choi BK, Hur SJ. Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products. Korean J Food Sci Anim Resour 2016;36(3):319-25.
        doi: 10.5851/kosfa.2016.36.3.319pubmed: 27433102google scholar: lookup
      30. Olson ME, Ralston B, Burwash L, Matheson-Bird H, Allan ND. Efficacy of oral meloxicam suspension for prevention of pain and inflammation following band and surgical castration in calves. BMC Vet Res 2016 Jun 13;12(1):102.
        doi: 10.1186/s12917-016-0735-3pubmed: 27295955google scholar: lookup
      31. Reddyjarugu B, Pavek T, Southard T, Barry J, Singh B. Analgesic Efficacy of Firocoxib, a Selective Inhibitor of Cyclooxygenase 2, in a Mouse Model of Incisional Pain. J Am Assoc Lab Anim Sci 2015 Jul;54(4):405-10.
        pubmed: 26224441
      32. Vivancos M, Barker J, Engbers S, Fischer C, Frederick J, Friedt H, Rybicka JM, Stastny T, Banse H, Cribb AE. Pharmacokinetics and bioequivalence of 2 meloxicam oral dosage formulations in healthy adult horses. Can Vet J 2015 Jul;56(7):730-6.
        pubmed: 26130835
      33. Newby NC, Renaud D, Tremblay R, Duffield TF. Evaluation of the effects of treating dairy cows with meloxicam at calving on retained fetal membranes risk. Can Vet J 2014 Dec;55(12):1196-9.
        pubmed: 25477550
      34. El-Hewaity M. Influence of flunixin on the disposition kinetic of cefepime in goats. Adv Pharmacol Sci 2014;2014:471517.
        doi: 10.1155/2014/471517pubmed: 24883058google scholar: lookup
      35. Guedes AG, Morisseau C, Sole A, Soares JH, Ulu A, Dong H, Hammock BD. Use of a soluble epoxide hydrolase inhibitor as an adjunctive analgesic in a horse with laminitis. Vet Anaesth Analg 2013 Jul;40(4):440-8.
        doi: 10.1111/vaa.12030pubmed: 23463912google scholar: lookup
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