Clinical Effect of Multidose Oral Administration of Firocoxib and t-TUCB Alone and in Combination for the Treatment of Naturally Occurring Osteoarthritis in Horses

Abstract

Introduction: Osteoarthritis is a degenerative and debilitating joint disease. Development of effective new drugs without adverse side effects is important for improving animal welfare. Soluble epoxide hydrolase (sEH) inhibitors represent an alternative method of pharmaceutical pain control that could be used alone or synergistically with nonsteroidal anti-inflammatory drugs (NSAIDs). The objective of the study was to evaluate the clinical effect of the sEH inhibitor, trans-4-{4-[3-(4-trifluro-methoxy-phenyl)-ureido]-cyclohexyloxy}-benzoic acid (t-TUCB), compared to the NSAID, firocoxib, in horses with osteoarthritis.

Methods: Six horses with radiographic evidence of tarsal osteoarthritis were utilized. A 3-way crossover study was performed with 10 days each of oral administration of (1) t-TUCB (500 mg), (2) firocoxib (57 mg), and (3) t-TUCB/firocoxib (500 mg/28.5 mg). Lameness evaluations utilizing a body-mounted inertial sensor system (Equinosis Q) and gastroscope exams were conducted before and following treatment periods.

Results: Gastric grades did not differ between or within treatment. Lameness grades significantly improved from baseline across all treatments (p < 0.05). Lameness grades remained improved from baseline 2 weeks following discontinuation of t-TUCB alone and in combination with firocoxib (p < 0.05). Lameness grades returned to baseline 2 weeks after discontinuation of firocoxib. No adverse events occurred.

Discussion/Conclusion: Treatment with t-TUCB resulted in improved objective lameness grades on par with firocoxib in horses with osteoarthritis. Lameness grades following discontinuation of t-TUCB with or without firocoxib remained improved from baseline, supporting the hypothesis that sEH inhibitors may represent a disease-modifying treatment of osteoarthritis. The sEH inhibitor, t-TUCB, is a promising novel analgesic for horses with osteoarthritis when used alone or synergistically with NSAIDs.

Acknowledgements: Funding was provided by a University of Tennessee Graduate School Student Faculty Research Award. The novel compound was provided by EicOsis.

The authors would like to acknowledge J. Smith for guidance on pharmacokinetics and K. G. Kerr, L. Gray, J. Levy, S. Streett, and A. Womble for assistance with data collection.

 

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Publikationsverlauf

Artikel online veröffentlicht:
16. September 2024