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Pharmacology of drugs used to treat osteoarthritis in veterinary practice

Abstract

As in humans, pain in animals may be associated with a wide range of conditions and circumstances, ranging from acute trauma to joint diseases. Joint diseases are common in companion animal medicine (horse, dog, cat) and at least 80% of cases are classified as osteoarthritis (OA). Several drug classes are available for OA therapy, including corticosteroids, non-steroidal antiinflammatory drugs (NSAIDs), agents with potential disease modifying properties and nutraceuticals. For long-term maintenance OA treatment, particularly in the horse and dog, NSAIDs are routinely and extensively used. This review outlines the pharmacokinetics (PK) and pharmacodynamics (PD) of NSAIDs in companion and farm animal species. NSAID PK and PD have been studied in models of acute inflammation, which enable use of PK-PD modeling to facilitate (a) studies of mechanism of action at the molecular level and (b) prediction of dosages for clinical use. The PK-PD approach is a powerful but underutilized tool which also facilitates inter-species comparisons.

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REFERENCES

  • Arifah, K. A., et al. (2003). Pharmacodynamics, chiral pharmacokinetics and PK-PD modeling of ketoprofen in the goat, J. Vet. Pharmacol. Ther. 26, 139–150.

    PubMed  Google Scholar 

  • Arifah, K. A. and Lees, P. (2002). Pharmacodynamics and pharmacokinetics of phenylbutazone in calves, J. Vet. Pharmacol. Ther. 25, 299–309.

    PubMed  Google Scholar 

  • Arifah, K. A., et al. (2001). Pharmacodynamics and pharmacokinetics of ketoprofen enantiomers in sheep, Am. J. Vet. Res. 62, 77–86.

    PubMed  Google Scholar 

  • Armstrong, S. and Lees, P. (1999). Effects of R and S enantiomers and a racemic mixture of carprofen on the production and release of proteoglycan and prostaglandinE2 from equine chondrocytes and cartilage explants, Am. J. Vet. Res. 60, 98–104.

    PubMed  Google Scholar 

  • Armstrong, S. and Lees, P. (2002). Effects of carprofen (R and S enantiomers and racemate) on the production of IL-1, IL-6 and TNF-α by equine chondrocytes and synoviocytes, J. Vet. Pharmacol. Ther. 25, 145–153.

    PubMed  Google Scholar 

  • Benton, H. P., et al. (1997). Effect of carprofen on sulfated glycosaminoglycan metabolism, protein synthesis, and prostaglandin release by cultured osteoarthritic canine chondrocytes, Am. J. Vet. Res. 58, 286–292.

    PubMed  Google Scholar 

  • Brideau, C. and Van Staden, C. (2001). In vitro effects of cyclooxygenase inhibitors in whole blood of horses, dogs and cats, Am. J. Vet. Res. 62, 1755–1760.

    PubMed  Google Scholar 

  • Bryant, C. E., et al. (2003). Evaluation of the ability of carprofen and flunixin meglumine to inhibit activation of nuclear factor kappa B, Am. J. Vet. Res. 64, 211–215.

    PubMed  Google Scholar 

  • Flecknell, P. A. and Waterman-Pearson, A. (2000). Pain management in animals. W.B. Saunders, London.

    Google Scholar 

  • Frean, S. P. and Lees, P. (2000). Effects of polysulfated glycosaminoglycan and hyaluronan on prostaglandin E2 production by cultured equine synoviocytes, Am. J. Vet. Res. 61, 499–505.

    PubMed  Google Scholar 

  • Frean, S. P., et al. (1999). In vitro stimulation of equine articular cartilage proteoglycan synthesis by hyaluronan and carprofen, Res. Vet. Sci. 67, 181–188.

    Google Scholar 

  • Frean, S. P., et al. (2000). Influence of interleukin-1β and hyaluronan on proteoglycan release from equine navicular hyaline cartilage and fibrocartilage, J. Vet. Pharmacol. Ther. 23, 67–72.

    PubMed  Google Scholar 

  • Frean, S. P., et al. (2002). Effects of anti-arthritic drugs on proteoglycan synthesis by equine cartilage, J. Vet. Pharmacol. Ther. 25, 289–298.

    PubMed  Google Scholar 

  • Frisbie, D. D., et al. (1997). Effects of triamcinolone acetonide on an in vivo equine osteochondral fragment exercise model, Equine Vet. J. 29, 349–359.

    PubMed  Google Scholar 

  • Giraudel, J. M., et al. (2003). Development and application of in vitro assays for the evaluation of inhibitors of constitutive and inducible cyclooxygenase, J. Vet. Pharmacol. Ther. 26 (Suppl. 1), 173–174.

    PubMed  Google Scholar 

  • Higgins, A. J., et al. (1984). Tissue-cage model for the collection of inflammatory exudate in ponies, Res. Vet. Sci. 36, 284–289.

    PubMed  Google Scholar 

  • Higgins, A. J., et al. (1987a). Studies on the use of a novel non-steroidal anti-inflammatory drug in the horse, Equine Vet. J. 19, 60–66.

    PubMed  Google Scholar 

  • Higgins, A. J., et al. (1987b). Actions of BW 540C in an equine model of acute inflammation: a pre-liminary study, Vet. Q. 9, 103–110.

    PubMed  Google Scholar 

  • Holton, L. L., et al. (1998). Comparison of three methods used for assessment of pain in dogs, J. Am. Vet. Med. Ass. 212, 61–66.

    Google Scholar 

  • Landoni, M. F., et al. (1995a). Pharmacokinetics and pharmacodynamics of ketoprofen in calves applying PK/ PD modeling, J. Vet. Pharmacol. Ther. 18, 315–324.

    PubMed  Google Scholar 

  • Landoni, M. F., et al. (1995b). Determination of pharmacokinetics and pharmacodynamics of flunixin in calves by use of pharmacokinetic/ pharmacodynamic modeling, Am. J. Vet. Res. 56, 786–793.

    PubMed  Google Scholar 

  • Landoni, M. F., et al. (1996). Pharmacokinetics and pharmacodynamics of tolfenamic acid in calves, Res. Vet. Sci. 61, 26–32.

    PubMed  Google Scholar 

  • Landoni, M. F. and Lees, P. (1995a). Comparison of the anti-inflammatory actions of flunixin and ketoprofen in horses applying PK/ PD modeling, Equine Vet. J. 27, 247–256.

    PubMed  Google Scholar 

  • Landoni, M. F. and Lees, P. (1995b). Pharmacokinetics/ and pharmacodynamics of ketoprofen enantiomers in calves, Chirality 7, 586–597.

    PubMed  Google Scholar 

  • Landoni, M. F., et al. (1999). Enantiospecific pharmacokinetics and pharmacodynamics of ketoprofen in sheep, J. Vet. Pharmacol. Ther. 22, 349–359.

    PubMed  Google Scholar 

  • Lees, P., et al. (1988a). In vitro and in vivo studies on the binding of phenylbutazoneand related drugs to equine feeds and digesta, Res. Vet. Sci. 44, 50–56.

    PubMed  Google Scholar 

  • Lees, P., et al. (1988b). Pharmacokinetics, metabolism and excretion of phenylbutazone in cattle following intravenous, intramuscular and oral administration, Res. Vet. Sci. 44, 57–67.

    PubMed  Google Scholar 

  • Lees, P., et al. (1999). Pharmacology and therapeutics of joint diseases. Cont. Prof. Dev. Vet. Med. 2, 18–26.

    Google Scholar 

  • Lees, P., et al. (1999). A pharmacodynamic and pharmacokinetics study with vedaprofen in an equine model of acute nonimmune inflammation, J. Vet. Pharmacol. Ther. 22, 96–106.

    PubMed  Google Scholar 

  • Lees, P., et al. (2000). New insights into inflammation with particular reference to the role of COX enzymes. 8th EAVPT International Congress, J. Vet. Pharmacol. Ther. (Suppl).

  • Lees, P., et al. (2002). Pharmacodynamics and enantioselective pharmacokinetics of racemic carpro-fen in the horse, J. Vet. Pharmacol. Ther. 25, 433–448.

    PubMed  Google Scholar 

  • Lipscomb, V. J., et al. (2002). Clinical efficacy and pharmacokinetics of carprofen in the treatment of dogs with osteoarthritis, Vet. Rec. 150, 684–689.

    PubMed  Google Scholar 

  • Maitho, T. E., et al. (1986). Absorption and pharmacokinetics of phenylbutazone in Welsh Mountain ponies, J. Vet. Pharmacol. Ther. 9, 26–39.

    PubMed  Google Scholar 

  • Millis, D. L., et al. (2002). Effect of Deracoxib, a New COX-2 inhibitor, on the preventionof lameness induced by chemical synovitis in dogs, Vet. Ther. 3, 453–464.

    PubMed  Google Scholar 

  • Pelletier, J. P., et al. (2000). Carprofen simultaneously reduces progression of morphological changes in cartilage and subchondral bone in experimental dog osteoarthritis, J. Rheum. 27, 2893–2902.

    PubMed  Google Scholar 

  • Sidhu, P., et al. (2003). Tissue chamber model of acute inflammation in farm animal species, Res. Vet. Sci. 74, 67–77.

    PubMed  Google Scholar 

  • Soraci, A., et al. (1995). Enantioselective glucuronidation and subsequent biliary excretion of carprofen in horses, Am. J. Vet. Res. 56, 358–361.

    PubMed  Google Scholar 

  • Streppa, H. K., et al. (2002). Cyclooxygenase selectivity of nonsteroidal anti-inflammatory drugs in canine blood, Am. J. Vet. Res. 63, 91–94.

    Google Scholar 

  • Toutain, P. L. (2003). Pharmacokinetics/ pharmacodynamics integration in dosage regimen opti-mization for veterinary medicine, J. Vet. Pharmacol. Ther. 26 (Suppl. 1), 1–8.

    Google Scholar 

  • Toutain, P. L., et al. (1994). Plasma concentrations and therapeutic efficacy of phenylbutazone and flunixin meglumine in the horse: pharmacokinetic/ pharmacodynamic modeling, J. Vet. Pharmacol. Ther. 17, 459–469.

    PubMed  Google Scholar 

  • Toutain, P. L., et al. (2001a). Pharmacokinetic profile and in vitro selective cyclooxygenase-2 inhibition by nimesulide in the dog, J. Vet. Pharmacol. Ther. 24, 35–42.

    PubMed  Google Scholar 

  • Toutain, P. L., et al. (2001b). A pharmacokinetic/ pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox-2 selective nonsteroidal anti-inflammatory drug in the dog, J. Vet. Pharmacol. Ther. 24, 43–55.

    PubMed  Google Scholar 

  • Wallace, J. L., et al. (1998). Cyclooxygenase1 contributesto inflammatory responses in rats and mice: Implications for gastrointestinal toxicity, Gastroenterology 115, 101–109.

    PubMed  Google Scholar 

  • Warner, T. D., et al. (1999). Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis, Proc. Natl. Acad. Sci. USA 96, 7563–7568.

    PubMed  Google Scholar 

  • Welsh, J. C. M., et al. (1992). Influence of feeding schedule on the absorption of orally administered flunixin in the horse, Equine Vet. J. (Suppl.) 11, 62–65.

    Google Scholar 

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Lees, P. Pharmacology of drugs used to treat osteoarthritis in veterinary practice. Inflammopharmacology 11, 385–399 (2003). https://doi.org/10.1163/156856003322699564

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  • DOI: https://doi.org/10.1163/156856003322699564

  • PAIN
  • OSTEOARTHRITIS
  • HORSE
  • DOG
  • RUMINANTS
  • NSAIDS
  • PK-PD MODELING