Comparison of two inhibitors of E-type prostanoid receptor four and carprofen in dogs with experimentally induced acute synovitis

Am J Vet Res. 2019 Nov;80(11):1001-1006. doi: 10.2460/ajvr.80.11.1001.

Abstract

Objective: To investigate the ability of a proprietary antagonist of E-type prostanoid receptor (EP) 4, grapiprant, and carprofen to attenuate lameness attributable to urate-induced synovitis in dogs.

Animals: 5 purpose-bred hound-cross dogs.

Procedures: A blinded, 3-way crossover study was performed. Dogs received each of 3 treatments (L-766, a proprietary antagonist of EP4; 4.0 mg/kg), grapiprant (an antagonist of EP4; 2.0 mg/kg), and carprofen (4.4 mg/kg); dogs received 4 doses of each treatment (14 and 2 hours before and 22 and 46 hours after urate injection). Synovitis was induced by intra-articular injection of sodium urate. Measurements (vertical ground reaction forces and clinical lameness scores) were obtained immediately before (0 hours; baseline) and 6, 12, 24, 36, and 48 hours after sodium urate injection. All data were analyzed with repeated-measures ANOVA.

Results: Lameness scores at 6 hours were significantly higher than baseline lameness scores for all treatments. Lameness scores for the grapiprant treatment remained significantly higher at 12 and 24 hours, compared with baseline lameness scores. Lameness scores for the carprofen treatment were significantly lower than lameness scores for the grapiprant treatment at 6, 12, and 24 hours. Analysis of peak vertical force and vertical impulse data revealed a pattern similar to that for lameness scores. Treatment with L-766 resulted in a significantly higher vertical impulse at 48 hours than did treatment with carprofen or grapiprant.

Conclusions and clinical relevance: In these dogs, carprofen was the most effective treatment for attenuating lameness induced by injection of sodium urate, and grapiprant was the least effective treatment.

Publication types

  • Comparative Study
  • Randomized Controlled Trial, Veterinary

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use*
  • Cross-Over Studies
  • Dog Diseases / drug therapy*
  • Dogs
  • Gait
  • Injections, Intra-Articular / veterinary
  • Lameness, Animal / chemically induced
  • Lameness, Animal / drug therapy*
  • Male
  • Receptors, Prostaglandin E, EP4 Subtype / antagonists & inhibitors*
  • Single-Blind Method
  • Sulfonylurea Compounds / therapeutic use*
  • Synovitis / chemically induced
  • Synovitis / drug therapy
  • Synovitis / veterinary*
  • Uric Acid

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbazoles
  • Receptors, Prostaglandin E, EP4 Subtype
  • Sulfonylurea Compounds
  • Uric Acid
  • carprofen
  • grapiprant