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American journal of veterinary research2001; 62(11); 1755-1760; doi: 10.2460/ajvr.2001.62.1755

In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats.

Abstract: To determine potency and selectivity of nonsteroidal anti-inflammatory drugs (NSAID) and cyclooxygenase- (COX-) specific inhibitors in whole blood from horses, dogs, and cats. Methods: Blood samples from 30 healthy horses, 48 healthy dogs, and 9 healthy cats. Methods: Activities of COX-1 and COX-2 were determined by measuring coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in whole blood with and without the addition of various concentrations of phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, carprofen, 5-bromo-2[4-fluorophenyl]-3-14-methylsulfonylphenyl]-thiophene (DuP 697), 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furan one (DFU), 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2-(5H)-furanone (MF-tricyclic), and celecoxib. Potency of each test compound was determined by calculating the concentration that resulted in inhibition of 50% of COX activity (IC50). Selectivity was determined by calculating the ratio of IC50 for COX-1 to IC50 for COX-2 (COX-1/COX-2 ratio). Results: The novel compound DFU was the most selective COX-2 inhibitor in equine, canine, and feline blood; COX-1/COX-2 ratios were 775, 74, and 69, respectively. Carprofen was the weakest inhibitor of COX-2, compared with the other COX-2 selective inhibitors, and did not inhibit COX-2 activity in equine blood. In contrast, NSAID such as phenylbutazone and flunixin meglumine were more potent inhibitors of COX-1 than COX-2 in canine and equine blood. Conclusions: The novel COX-2 inhibitor DFU was more potent and selective in canine, equine, and feline blood, compared with phenylbutazone, flunixin meglumine, and carprofen. Compounds that specifically inhibit COX-2 may result in a lower incidence of adverse effects, compared with NSAID, when administered at therapeutic dosages to horses, dogs, and cats.
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Publication Date: 2001-11-13 PubMed ID: 11703020DOI: 10.2460/ajvr.2001.62.1755Google Scholar: Lookup
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Summary

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The study assesses the effectiveness and selectivity of different non-steroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase inhibitors on horses, dogs, and cats. The experimental compound DFU was found to be the most potent and selective COX-2 inhibitor in all three animal types, potentially leading to fewer adverse effects compared to regular NSAIDs.

Research Methodology

  • Blood samples were collected from 30 healthy horses, 48 healthy dogs, and 9 healthy cats.
  • The researchers then measured the effect of various NSAIDs and COX inhibitors, including phenylbutazone, flunixin meglumine, ketoprofen, diclofenac, indomethacin, meloxicam, carprofen, DuP 697, DFU, MF-tricyclic, and celecoxib, on COX-1 and COX-2 activities in the blood samples.
  • This was done by recording the coagulation-induced thromboxane and lipopolysaccharide-induced prostaglandin E2 concentrations, respectively, in the blood with and without the added drugs.
  • The potency and selectivity of each drug were determined by calculating the concentration that brought about the inhibition of 50% of COX activity (IC50), and the ratio of IC50 for COX-1 to IC50 for COX-2 (COX-1/COX-2 ratio), respectively.

Results and Implications

  • The novel compound DFU emerged as the most potent and selective COX-2 inhibitor in the blood of all three animal types, with COX-1/COX-2 ratios of 775 (horses), 74 (dogs), and 69 (cats).
  • In comparison, carprofen was the weakest inhibitor of COX-2 among the other COX-2 selective inhibitors and did not inhibit COX-2 activity in horse blood at all.
  • Conventional NSAIDs such as phenylbutazone and flunixin meglumine, on the other hand, were more potent inhibitors of COX-1 than COX-2 in the blood of dogs and horses.
  • These findings suggest that drugs specifically designed to inhibit COX-2, such as DFU, could be more effective and cause fewer side effects than regular NSAIDs when administered to horses, dogs, and cats.
  • Further research and clinical trials are necessary to confirm the potential benefits and safety of these COX-2 specific inhibitors for veterinary use.

Cite This Article

APA
Brideau C, Van Staden C, Chan CC. (2001). In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs, and cats. Am J Vet Res, 62(11), 1755-1760. https://doi.org/10.2460/ajvr.2001.62.1755

Publication

American journal of veterinary research
ISSN: 0002-9645
NlmUniqueID: 0375011
Country: United States
Language: English
Volume: 62
Issue: 11
Pages: 1755-1760

Researcher Affiliations

Brideau, C
  • Department of Biochemistry, Merck Frosst Centre for Therapeutic Research, Kirkland, Q, Canada.
Van Staden, C
    Chan, C C

      MeSH Terms

      • Animals
      • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
      • Carbazoles / pharmacology
      • Cats / blood
      • Clonixin / analogs & derivatives
      • Clonixin / pharmacology
      • Cyclooxygenase 1
      • Cyclooxygenase 2
      • Cyclooxygenase 2 Inhibitors
      • Cyclooxygenase Inhibitors / pharmacology
      • Dinoprostone / biosynthesis
      • Dinoprostone / blood
      • Dogs / blood
      • Female
      • Furans / pharmacology
      • Horses / blood
      • Inhibitory Concentration 50
      • Isoenzymes / antagonists & inhibitors
      • Isoenzymes / blood
      • Male
      • Phenylbutazone / pharmacology
      • Prostaglandin-Endoperoxide Synthases / blood
      • Thromboxane B2 / biosynthesis
      • Thromboxane B2 / blood

      Citations

      This article has been cited 34 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. Mag P, Nemes-Terényi M, Jerzsele Á, Mátyus P. Some Aspects and Convergence of Human and Veterinary Drug Repositioning. Molecules 2024 Sep 20;29(18).
        doi: 10.3390/molecules29184475pubmed: 39339469google scholar: lookup
      3. 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
      4. 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
      5. Mota-Rojas D, Velarde A, Marcet-Rius M, Orihuela A, Bragaglio A, Hernández-Ávalos I, Casas-Alvarado A, Domínguez-Oliva A, Whittaker AL. Analgesia during Parturition in Domestic Animals: Perspectives and Controversies on Its Use. Animals (Basel) 2022 Oct 6;12(19).
        doi: 10.3390/ani12192686pubmed: 36230426google scholar: lookup
      6. Paterson EA, Turner PV. Challenges with Assessing and Treating Pain in Research Primates: A Focused Survey and Literature Review. Animals (Basel) 2022 Sep 5;12(17).
        doi: 10.3390/ani12172304pubmed: 36078024google scholar: lookup
      7. 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
      8. Solà J, Menargues À, Homedes J, Salichs M, Álvarez I, Romero L, Vela JM. Selective inhibition of cyclooxygenase-2 by enflicoxib, its enantiomers and its main metabolites in vitro in canine blood. J Vet Pharmacol Ther 2022 May;45(3):235-244.
        doi: 10.1111/jvp.13042pubmed: 35038171google scholar: lookup
      9. 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
      10. 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
      11. Bassiouni W, Daabees T, Norel X, Senbel AM. Hypoactivity of rat detrusor muscle in a model of cystitis: exacerbation by non-selective COX inhibitors and amelioration by a selective DP(1) receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol 2019 Apr;392(4):437-450.
        doi: 10.1007/s00210-018-01599-7pubmed: 30552456google scholar: lookup
      12. Kongara K, Chambers JP. Robenacoxib in the treatment of pain in cats and dogs: safety, efficacy, and place in therapy. Vet Med (Auckl) 2018;9:53-61.
        doi: 10.2147/VMRR.S170893pubmed: 30148083google scholar: lookup
      13. Martin EM, Jones SL. Inhibition of microsomal prostaglandin E-synthase-1 (mPGES-1) selectively suppresses PGE(2) in an in vitro equine inflammation model. Vet Immunol Immunopathol 2017 Oct;192:33-40.
        doi: 10.1016/j.vetimm.2017.09.008pubmed: 29042013google scholar: lookup
      14. 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
      15. Buntenkötter K, Osmers M, Schenk I, Schänzer W, Machnik M, Düe M, Kietzmann M. Pharmacokinetics and in vitro efficacy of salicylic acid after oral administration of acetylsalicylic acid in horses. BMC Vet Res 2017 Jan 19;13(1):28.
        doi: 10.1186/s12917-017-0955-1pubmed: 28103874google scholar: lookup
      16. Silver K, Littlejohn A, Thomas L, Marsh E, Lillich JD. Inhibition of Kv channel expression by NSAIDs depolarizes membrane potential and inhibits cell migration by disrupting calpain signaling. Biochem Pharmacol 2015 Dec 15;98(4):614-28.
        doi: 10.1016/j.bcp.2015.10.017pubmed: 26549367google scholar: lookup
      17. 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
      18. Schlapp G, Goyeneche L, Fernández G, Menchaca A, Crispo M. Administration of the nonsteroidal anti-inflammatory drug tolfenamic acid at embryo transfer improves maintenance of pregnancy and embryo survival in recipient mice. J Assist Reprod Genet 2015 Feb;32(2):271-5.
        doi: 10.1007/s10815-014-0378-xpubmed: 25561155google scholar: lookup
      19. 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
      20. Bates JL, Karriker LA, Stock ML, Pertzborn KM, Baldwin LG, Wulf LW, Lee CJ, Wang C, Coetzee JF. Impact of transmammary-delivered meloxicam on biomarkers of pain and distress in piglets after castration and tail docking. PLoS One 2014;9(12):e113678.
        doi: 10.1371/journal.pone.0113678pubmed: 25437866google scholar: lookup
      21. Bauer C, Frost P, Kirschner S. Pharmacokinetics of 3 formulations of meloxicam in cynomolgus macaques (Macaca fascicularis). J Am Assoc Lab Anim Sci 2014 Sep;53(5):502-11.
        pubmed: 25255073
      22. Ingrao JC, Johnson R, Tor E, Gu Y, Litman M, Turner PV. Aqueous stability and oral pharmacokinetics of meloxicam and carprofen in male C57BL/6 mice. J Am Assoc Lab Anim Sci 2013 Sep;52(5):553-9.
        pubmed: 24041210
      23. Barton MH, Paske E, Norton N, King D, Giguère S, Budsberg S. Efficacy of cyclo-oxygenase inhibition by two commercially available firocoxib products in horses. Equine Vet J 2014 Jan;46(1):72-5.
        doi: 10.1111/evj.12095pubmed: 23662599google scholar: lookup
      24. DiVincenti L Jr. Analgesic use in nonhuman primates undergoing neurosurgical procedures. J Am Assoc Lab Anim Sci 2013 Jan;52(1):10-6.
        pubmed: 23562027
      25. Kreuder AJ, Coetzee JF, Wulf LW, Schleining JA, KuKanich B, Layman LL, Plummer PJ. Bioavailability and pharmacokinetics of oral meloxicam in llamas. BMC Vet Res 2012 Jun 21;8:85.
        doi: 10.1186/1746-6148-8-85pubmed: 22720782google scholar: lookup
      26. Malreddy PR, Coetzee JF, Kukanich B, Gehring R. Pharmacokinetics and milk secretion of gabapentin and meloxicam co-administered orally in Holstein-Friesian cows. J Vet Pharmacol Ther 2013 Feb;36(1):14-20.
        doi: 10.1111/j.1365-2885.2012.01384.xpubmed: 22372845google scholar: lookup
      27. Friess SH, Naim MY, Kilbaugh TJ, Ralston J, Margulies SS. Premedication with meloxicam exacerbates intracranial haemorrhage in an immature swine model of non-impact inertial head injury. Lab Anim 2012 Apr;46(2):164-6.
        doi: 10.1258/la.2011.011084pubmed: 22238292google scholar: lookup
      28. Gunew MN, Menrath VH, Marshall RD. Long-term safety, efficacy and palatability of oral meloxicam at 0.01-0.03 mg/kg for treatment of osteoarthritic pain in cats. J Feline Med Surg 2008 Jul;10(3):235-41.
        doi: 10.1016/j.jfms.2007.10.007pubmed: 18440263google scholar: lookup
      29. Freeman LC, Narvaez DF, McCoy A, von Stein FB, Young S, Silver K, Ganta S, Koch D, Hunter R, Gilmour RF, Lillich JD. Depolarization and decreased surface expression of K+ channels contribute to NSAID-inhibition of intestinal restitution. Biochem Pharmacol 2007 Jun 30;74(1):74-85.
        doi: 10.1016/j.bcp.2007.03.030pubmed: 17499219google scholar: lookup
      30. Cuthbert R, Parry-Jones J, Green RE, Pain DJ. NSAIDs and scavenging birds: potential impacts beyond Asia's critically endangered vultures. Biol Lett 2007 Feb 22;3(1):90-3.
        doi: 10.1098/rsbl.2006.0554pubmed: 17443974google scholar: lookup
      31. Wibberley A, McCafferty GP, Evans C, Edwards RM, Hieble JP. Dual, but not selective, COX-1 and COX-2 inhibitors, attenuate acetic acid-evoked bladder irritation in the anaesthetised female cat. Br J Pharmacol 2006 May;148(2):154-61.
        doi: 10.1038/sj.bjp.0706715pubmed: 16547526google scholar: lookup
      32. Montoya L, Ambros L, Kreil V, Bonafine R, Albarellos G, Hallu R, Soraci A. A pharmacokinetic comparison of meloxicam and ketoprofen following oral administration to healthy dogs. Vet Res Commun 2004 Jul;28(5):415-28.
        doi: 10.1023/b:verc.0000034995.81994.49pubmed: 15379436google scholar: lookup
      33. Lees P. Pharmacology of drugs used to treat osteoarthritis in veterinary practice. Inflammopharmacology 2003;11(4):385-99.
        doi: 10.1163/156856003322699564pubmed: 15035792google scholar: lookup
      34. Arumugam TV, Arnold N, Proctor LM, Newman M, Reid RC, Hansford KA, Fairlie DP, Shiels IA, Taylor SM. Comparative protection against rat intestinal reperfusion injury by a new inhibitor of sPLA2, COX-1 and COX-2 selective inhibitors, and an LTC4 receptor antagonist. Br J Pharmacol 2003 Sep;140(1):71-80.
        doi: 10.1038/sj.bjp.0705402pubmed: 12967936google scholar: lookup
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