deracoxib and Synovitis

This positive-control study evaluated the efficacy of firocoxib versus carprofen, deracoxib, and meloxicam for the prevention of pain and inflammation in a urate crystal synovitis model of lameness. Lameness scoring and force plate gait analysis were used to assess efficacy. The resulting lameness scores and force plate ground reaction forces after urate crystal injection were not significantly different among the groups. Relative to each group's baseline (nonlame) score, only the firocoxib group was not significantly lame, based on lameness score, at the model's peak effect.

Topics: 4-Butyrolactone; Animals; Carbazoles; Cyclooxygenase 2 Inhibitors; Dog Diseases; Dogs; Female; Lameness, Animal; Male; Meloxicam; Severity of Illness Index; Sulfonamides; Sulfones; Synovitis; Thiazines; Thiazoles; Treatment Outcome; Uric Acid

Twenty-four healthy, mixed-breed hound-type dogs were evenly and randomly assigned to a placebo control group, one of four dosages of deracoxib (0.3, 1, 3, or 10 mg/kg), or carprofen (2.2 mg/kg). Oral dosing of placebo, carprofen, or deracoxib was done 30 minutes before intraarticular injection of urate crystal suspension for induction of synovitis. Ground reaction forces, subjective clinical lameness scores, pain, joint effusion, and quantitative pain threshold responses were measured in a blinded fashion before induction of synovitis and 2, 4, 6, 8, 12, and 24 hours after injection. The medium and high dosages of deracoxib were effective in preventing lameness and pain associated with synovitis. Carprofen was also somewhat effective in attenuating the severity of urate-induced synovitis but to a lesser degree than the medium dose of deracoxib. Preemptive deracoxib treatment at dosages as low as 1 mg/kg reduced lameness and pain of synovitis associated with intraarticular administration of urate crystals.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Hindlimb; Lameness, Animal; Male; Pain; Pain Measurement; Prospective Studies; Severity of Illness Index; Single-Blind Method; Sulfonamides; Synovitis; Treatment Outcome; Uric Acid

To evaluate the efficacy of epidurally administered deracoxib to mediate the signs of a sodium urate crystal-induced stifle synovitis in dogs, and to compare the efficacy of epidural versus subcutaneously administered deracoxib.. Experimental, randomized, blinded, placebo-controlled modified cross-over design.. Random source, adult, mixed breed dogs (n = 24; 14 males, 10 females).. Sodium urate crystals were used to create a stifle synovitis model to evaluate the efficacy of deracoxib. Dogs were divided into 4 groups: 3 mg/kg epidural deracoxib, 1.5 mg/kg epidural deracoxib, 3 mg/kg subcutaneous deracoxib, and a placebo (vehicle for deracoxib). Force plate and subjective evaluations were made at time 0, 2, 4, 8, 12, and 24 hours post-treatment. Repeated measures ANOVA with Bonferroni-corrected post hoc comparisons was used to determine significant treatment effects.. Peak vertical force (PVF) and vertical impulse (VI) were both significantly higher in deracoxib treated dogs compared with placebo. For 3 mg/kg epidural and subcutaneous deracoxib, PVF and VI were significantly greater than for 1.5 mg/kg epidural deracoxib. Overall pain score for all deracoxib-treated dogs was significantly lower than for placebo dogs.. Epidural administration of deracoxib is effective at providing analgesia in an acute joint pain model; however, it does not appear to be more effective than systemic administration.. Injectable deracoxib is effective in providing analgesia in acute inflammatory conditions of synovial joints.

Topics: Analgesics; Analysis of Variance; Animals; Cross-Over Studies; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Injections, Epidural; Injections, Subcutaneous; Male; Random Allocation; Stifle; Sulfonamides; Synovitis; Treatment Outcome; Uric Acid

To determine cyclooxygenase-2 (COX-2) selectivity, pharmacokinetic properties, and in vivo efficacy of ML-1,785,713 in dogs.. 21 healthy male and female mixed-breed dogs and 24 healthy male Beagles.. Selectivity of ML-1,785,713 for inhibiting COX-2 was determined by comparing the potency for inhibiting cyclooxygenase-1 (COX-1) with that of COX-2 in canine blood. Pharmacokinetic properties were determined after i.v. (2 mg/kg) and oral (8 mg/kg) administration in female mixed-breed dogs. In vivo efficacy was evaluated in male mixed-breed dogs with urate crystal-induced synovitis. Prophylactic efficacy was evaluated by administering ML-1,785,713 two hours before induction of synovitis whereas therapeutic efficacy was determined by administering ML-1,785,713 one hour after induction of synovitis.. Blood concentrations that resulted in 50% inhibition of COX-1 and COX-2 activity in vitro were 119.1 microM and 0.31 microM, respectively, and selectivity ratio for inhibiting COX-2 relative to COX-1 was 384. ML-1,785,713 had high oral bioavailability (101%), low systemic clearance (77 mL/min/kg), and an elimination half-life of 5.9 hours. ML-1,785,713 was efficacious when administered prophylactically and therapeutically to dogs with urate crystal-induced synovitis.. ML-1,785,713 is a novel, potent COX-2 inhibitor that is the most selective COX-2 inhibitor described for use in dogs to date. ML-1,785,713 has oral bioavailability and low systemic clearance that is comparable to other non-steroidal anti-inflammatory drugs. It is effective after prophylactic and therapeutic administration in attenuating lameness in dogs with urate crystal-induced synovitis. Drugs that specifically inhibit COX-2 and not COX-1 at therapeutic doses may have an improved tolerability profile, compared with nonselective non-steroidal anti-inflammatory drugs.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Sulfonamides; Sulfones; Synovitis