Skip to main content
PMC home page
Acta Veterinaria Scandinavica logoLink to Acta Veterinaria Scandinavica
. 1989 Mar 1;30(1):27–35. doi: 10.1186/BF03548065

Effects of Phenylbutazone and Indomethacin on the Post-operative Course following Experimental Orthopaedic Surgery in Dogs

Susan W Mbugua 14,24,✉, Lasse A Skoglund 14,24, Per Løkken 14,24
PMCID: PMC8142172  PMID: 2782230

Abstract

Randomized placebo-controlled crossover studies were carried out in dogs to evaluate how two non-steroidal antiinflammatory drugs (NSAID) might modulate an acute post-traumatic inflammatory reaction. Two “identical” surgical interventions were performed on the forelimbs of each animal with an interval of 28 days, to enable a paired comparison of the inflammatory signs and the wound/bone healing processes. At one operation 8 dogs received 300 mg phenylbutazone twice daily for 8 days starting on the day before surgery, and at the other operation matching placebo tablets were given. In a similar placebo-controlled trial another group of 8 dogs received 5 mg indomethacin twice daily. With phenylbutazone the post-operative swelling was not significantly reduced compared to placebo, but there was less pain and limping. With indomethacin the swelling was somewhat reduced, but there was no consistent difference to placebo in the pain and limping assessments. None of the drugs appeared to distinctly effect the wound or fracture healing, as evaluated by clinical inspection, comparison of radiographs and comparison of bone sections from the sites of surgery. It proved difficult to select an appropriate dosage of indomethacin due to its high potential to induce GI ulceration and bleeding in dogs. In this experimental surgical model with an acute inflammation, neither phenylbutazone nor indomethacin showed impressive anti-inflammatory or analgesic properties. In the same model paracetamol has proved to significantly and more efficiently, reduce both swelling and pain without any noticeable adverse effects, and appears to be a better alternative than the two presently tested NSAID.

Keywords: anti-inflammatory effects, swelling, pain, wound/bone healing

Full Text

The Full Text of this article is available as a PDF (1.6 MB).

Acknowledgements

This study was supported by the Norwegian Agency for International Development (NO-RAD). The authors are grateful to L. Sandvik (Ciba-Geigy Pharma A/S, Norway) for performing the statistical analyses and further for the valuable assistance offered by several staff members of the Department of Pharmacology and Toxicology, The Norwegian College of Veterinary Medicine.

References

  1. Album B, Olsen I, Lokken P. Bilateral surgical removal of impacted mandibular molar teeth as a model for drug evaluation: A test with oxyphenbutazone (Tanderil) Int. J. Oral Surg. 1977;6:177–189. doi: 10.1016/S0300-9785(77)80051-3. [DOI] [PubMed] [Google Scholar]
  2. Allgöwer M, Burri C, Graffenried P, Guber UF, Heim U, Meng J, Segmueller G, Siegrist J, Studer E. Quantitative analysis of the effect of anti-phlogistic substances in lower leg fractures. Schweiz. Med. Wochenschr. 1963;93:565–567. [PubMed] [Google Scholar]
  3. Amin MM, Engel BM, Laskin DM. Effect of indomethacin on postsurgical edema in rats. Oral Surg. 1983;55:244–246. doi: 10.1016/0030-4220(83)90321-3. [DOI] [PubMed] [Google Scholar]
  4. Dayton PG, Israili ZH, Perel JM. Influence of binding on drug metabolism and distribution. Ann. NY. Acad. Sci. 1973;226:172–194. doi: 10.1111/j.1749-6632.1973.tb20480.x. [DOI] [PubMed] [Google Scholar]
  5. Duggan DE, Hooke KF, Noll RM, Chiu K K. Enterohepatic circulation of indomethacin and its role in intestinal irritation. Biochem. Pharmacol. 1975;24:1749–1754. doi: 10.1016/0006-2952(75)90450-5. [DOI] [PubMed] [Google Scholar]
  6. Elves MV, Bayley I, Roylance PJ. The effect of indomethacin upon experimental fractures in the rat. Acta orthop. scand. 1982;53:35–41. doi: 10.3109/17453678208992176. [DOI] [PubMed] [Google Scholar]
  7. Frey H-H, Göbel W, Löscher W. Pharmacokinetics of primidone and its active metabolites in the dog. Arch. Int. Pharmacodyn. Therap. 1979;242:14–39. [PubMed] [Google Scholar]
  8. Goldie IF, Gunterberg B, Jacobson C. Foot volumetry as an objective test of the effect of antiphlogistic drugs in ankle sprains. Rheumatol. Rehabil. 1974;13:204–207. doi: 10.1093/rheumatology/13.4.204. [DOI] [PubMed] [Google Scholar]
  9. Higgins AJ. The biology, pathophysiology and control of eicosanoids in inflammation. J. vet. Pharmacol. Therap. 1985;8:1–18. doi: 10.1111/j.1365-2885.1985.tb00919.x. [DOI] [PubMed] [Google Scholar]
  10. Huskisson EC, Berry H, Street FG, Medhurst HE. Indomethacin for soft-tissue injuries. A double-blind study in football players. Rheumatol. Rehabil. 1973;12:159–160. doi: 10.1093/rheumatology/12.3.159. [DOI] [PubMed] [Google Scholar]
  11. Kaergaard NC, Stergaard EH, Frey H-H. Versuche zur Dosierung von Phenylbutazon beim Hund. (Dose experiments with phenylbutazone in the dog). Deutsch. Tierärtzl. Wochen- sebr. 1969;76:378–381. [PubMed] [Google Scholar]
  12. Lees P, Higgins AJ. Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse. Equine vet. J. 1985;17:83–96. doi: 10.1111/j.2042-3306.1985.tb02056.x. [DOI] [PubMed] [Google Scholar]
  13. Lehman EL, d’Abrera HJM. Non-parametrics: Statistical methods based on ranks. San Fransisco: Holden- Day; 1975. pp. 18–23. [Google Scholar]
  14. Lindner J. Diskussion (Discussion) In: J L, Wilhelm E, editors. Die post-traumatische Entzündung. (The post-traumatic inflammation) 1967. p. 221. [Google Scholar]
  15. Lokken P, Olsen I, Bruaset I, Norman-Pedersen K. Bilateral surgical removal of impacted lower third molar teeth as a model for drug evaluation: A test with ibuprofen. Eur. J. clin. Pharmacol. 1975;8:209–216. doi: 10.1007/BF00567117. [DOI] [PubMed] [Google Scholar]
  16. Lokken P, Skjelbred P. Analgesic and anti-inflammatory effects of paracetamol evaluated by bilateral oral surgery. Br. J. clin. Pharma col. 1980;10:253S–260S. doi: 10.1111/j.1365-2125.1980.tb01808.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lokken P, Skjelbred P. Aspirin or paracetamol? Lancet. 1981;ii:1346–1347. doi: 10.1016/S0140-6736(81)91366-0. [DOI] [PubMed] [Google Scholar]
  18. Mbugua SW, Skoglund LA, Skjelbred P, Lokken P. Effect of a glucocorticoid on the post-operative course following experimental orthopaedic surgery in dogs. Acta vet. scand. 1988;29:43–49. doi: 10.1186/BF03548390. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mburu DN, Mbugua SW, Skoglund LA, Lokken P. Effects of paracetamol and acetylsalicylic acid on the post-operative course after experimental orthopaedic surgery in dogs. J. vet. Pharmacol. Therap. 1988;11:163–171. doi: 10.1111/j.1365-2885.1988.tb00137.x. [DOI] [PubMed] [Google Scholar]
  20. Morger R. Oxyphenbutazone in Kaninchen-Modellversuch beim Volkmann-Syndrom. (Rabbit-model experiments with oxyphenbutazone in the Volkmann-syndrome) In: J L, Wilhelm E, editors. Die posttraumatische Entzündung. (The post-traumatic inflammation) 1967. pp. 45–50. [Google Scholar]
  21. Olesen E, Zachariae L. Absent effect of oxyphenbutazone (Tanderil) upon oedema following operation for Dupuytren’s contracture. Acta chir. scand. 1965;729:352–358. [PubMed] [Google Scholar]
  22. Peacock EE, Jr, van Winkle W., Jr . Wound repair. 1976. pp. 185–190. [Google Scholar]
  23. Penners R. Die Wirkung von Indomethacin auf das postoperative Ödem und die Wundheilung. (The effect of indomethacin on the post-operative oedema and wound healing). Arzneim.-Forsch. 1971;27:1842–1843. [PubMed] [Google Scholar]
  24. Petersen JK. Anti-inflammatory and analgesic effects of indomethacin following removal of impacted mandibular third molars. Int. J. Oral Surg. 1975;4:267–276. doi: 10.1016/S0300-9785(75)80044-5. [DOI] [PubMed] [Google Scholar]
  25. Pfeifer H. Klinische Beobachtungen über Knochenwundheilung unter Oxyphenbutazon. (Clinical observations of osseous wound healing with oxyphenbutazone) In: J L, Wilhelm E, editors. Die posttraumatische Entzündung. (The post-traumatic inflammation) 1967. pp. 213–220. [Google Scholar]
  26. Ruckebusch Y, Toutain PL. Non-steroidal antiinflammatory agents: Species differences in pharmacodynamics. Vet. Res. Com. 1983;7:359–368. doi: 10.1007/BF02228646. [DOI] [PubMed] [Google Scholar]
  27. Schiller R, De S J. Post-operative steroid injection: The first seventy-two hours of bone healing. J. Amer. Podiat. Assoc. 1979;69:364–366. doi: 10.7547/87507315-69-6-364. [DOI] [PubMed] [Google Scholar]
  28. Skjelbred P. The effects of acetylsalicylic acid on swelling, pain and other events after oral surgery. Brit. J. clin. Pharmacol. 1984;17:379–384. doi: 10.1111/j.1365-2125.1984.tb02361.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Skjelbred P, Lokken P. Post-operative pain and inflammatory reaction reduced by injection of a corticosteroid. A controlled test in bilateral oral surgery. Eur. J. clin. Pharmacol. 1982;21:391–396. doi: 10.1007/BF00542325. [DOI] [PubMed] [Google Scholar]
  30. Skjelbred P, Lokken P. Reduction of pain and swelling by a corticosteroid injection 3 hours after surgery. Eur. J. clin. Pharmacol. 1982;23:141–146. doi: 10.1007/BF00545968. [DOI] [PubMed] [Google Scholar]
  31. Skjelbred P, Lokken P, Skoglund LA. Post-operative administration of acetaminophen to reduce swelling and other inflammatory events. Curr. Ther. Res. 1984;35:377–385. [Google Scholar]
  32. Sudmann E, Dregelid E, Bessesen A, Morland J. Inhibition of fracture healing by indomethacin in rats. Eur. J. clin. Invest. 1979;9:333–339. doi: 10.1111/j.1365-2362.1979.tb00893.x. [DOI] [PubMed] [Google Scholar]
  33. Sudmann E, Hagen T. Indomethacin-induced delayed fracture healing. Arch. Orthop. Unfall- chir. 1976;85:151–154. doi: 10.1007/BF00415452. [DOI] [PubMed] [Google Scholar]
  34. Tabata K, Ohtsuki H, Okabe S. Role of lymphoid nodules in pathogenesis of indomethacin-induced gastric lesions in dogs. Dig. Dis. Sei. 1984;29:346–352. doi: 10.1007/BF01318521. [DOI] [PubMed] [Google Scholar]
  35. Teelmann K. Die Magen-Darm-Empfmdlichkeit des Hundes gegenüber nichtsteroidalen Anti- phlogistika/Antirheumatika. (Gastro-intestinal sensitivity for non-steroidal antiphlogistics/an- tirheumatics in the dog). Kleintierpraxis. 1983;28:177–188. [Google Scholar]
  36. Vinegar R, Truax JF. Pathways to inflammation II. Introduction to and philosophy of the symposium. Fed. Proc. 1982;41:2567–2568. [PubMed] [Google Scholar]
  37. Zederfeldt B, Gruber UF. Der Einfluss von Indomethacin auf Wundheilung. (The effect of indomethacin on wound healing) In: J L, Wilhelm E, editors. Die posttraumatische Entzündung. (The post-traumatic inflammation) Bern-Stuttgart: Hans Huber; 1967. pp. 51–55. [Google Scholar]

Articles from Acta Veterinaria Scandinavica are provided here courtesy of BMC

RESOURCES