cj-023-423 and Osteoarthritis

Grapiprant is the pioneer member of the novel piprant class, a potent and specific antagonist of the prostaglandin E2 receptor 4. It has been approved in veterinary medicine for the control of pain and inflammation associated with osteoarthritis in dogs at the dose regimen of 2 mg/kg once a day by the FDA and EMA (for pain only) in 2016 and 2018, respectively. The aim of this narrative review was to report the analytical methods, pharmacokinetics, pharmacodynamics and safety of grapiprant in several animal species using the best available published scientific evidence. In conclusion, most of the analytical methods proposed for grapiprant detection are simple, reliable, sensitive and validated. The pharmacokinetics show discrepancies between animal species. The therapeutic efficacy seems more suited to chronic rather than acute pain.

Topics: Animals; Dinoprostone; Dog Diseases; Dogs; Osteoarthritis; Pain; Sulfonylurea Compounds

This study evaluated the effectiveness and safety of grapiprant for treatment of pain in dogs with osteoarthritis (OA).. Grapiprant will relieve pain as measured by the owner's and veterinarian's evaluation of pain in dogs with OA. Another objective was evaluation of the safety of grapiprant.. Two hundred and eighty-five client-owned dogs with OA were enrolled and treated with grapiprant or placebo with 262 cases (N = 131 in each group) evaluable for the effectiveness analysis.. In this prospective, randomized, masked, placebo-controlled study dogs were treated daily with grapiprant (2 mg/kg) per OS or placebo. Owners completed an evaluation using the Canine Brief Pain Inventory (CBPI) on days 0, 7, 14, 21, and 28. Success was defined as improvement in the CBPI. Veterinary assessments were made on screening and days 14 and 28. Safety was evaluated by physical examination, evaluation of clinical pathology results, and owner observations.. Grapiprant treatment improved pain compared to placebo on day 28 (48.1 and 31.3% treatment successes respectively; P = .0315). The pain interference score (PIS) and pain severity score (PSS) improved in the grapiprant group compared to placebo (P = .0029 and 0.0022, respectively). Veterinary assessments were significantly better in the grapiprant-treated dogs (P = .0086). Grapiprant generally was well tolerated, but a higher percentage of treated dogs (17.02%) had occasional vomiting as compared to the placebo group (6.25%).. Grapiprant is an effective treatment for alleviation of pain in dogs with OA, and represents a modality of treatment that may be better tolerated than current options.

Topics: Animals; Dog Diseases; Dogs; Osteoarthritis; Pain; Receptors, Prostaglandin E, EP4 Subtype; Sulfonylurea Compounds; Vomiting

To investigate the safety of daily oral administration of grapiprant to dogs.. Thirty-six 9-month-old Beagles of both sexes.. Dogs were randomly assigned to groups that received grapiprant via oral gavage at 0, 1, 6, or 50 mg/kg (total volume, 5 mL/kg), q 24 h for 9 months. Each group contained 4 dogs of each sex (ie, 8 dogs/group), except for the 50 mg/kg group, which included 4 additional dogs that were monitored for an additional 30 days after treatment concluded (recovery period). All dogs received ophthalmologic, ECG, and laboratory evaluations before treatment began (baseline) and periodically afterward. All dogs were observed daily. Dogs were euthanized at the end of the study for necropsy and histologic evaluation.. All dogs remained clinically normal during treatment, with no apparent changes in appetite or demeanor. Emesis and soft or mucoid feces that occasionally contained blood were observed in all groups, although these findings were more common in dogs that received grapiprant. In general, clinicopathologic findings remained within baseline ranges. Drug-related changes in serum total protein and albumin concentrations were detected, but differences were small and resolved during recovery. No drug-related gross or microscopic pathological changes were detected in tissue samples except mild mucosal regeneration in the ileum of 1 dog in the 50 mg/kg group.. Results suggested the safety of long-term oral administration of grapiprant to dogs. Efficacy of grapiprant in the treatment of dogs with osteoarthritis needs to be evaluated in other studies.

Topics: Administration, Oral; Animals; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Female; Male; Osteoarthritis; Pain Measurement; Sulfonylurea Compounds; Treatment Outcome

Topics: Animals; Dog Diseases; Dogs; Osteoarthritis; Pain; Pain Management; Sulfonylurea Compounds; Sus scrofa; Swine; Swine Diseases

Topics: Animals; Dinoprostone; Dogs; Humans; Osteoarthritis; Pain; Pain Management; Pilot Projects; Rats; Receptors, Prostaglandin E, EP4 Subtype; Sulfonylurea Compounds

Grapiprant is the novel selective EP4 receptor inhibitor recently issued on the veterinary market for dogs affected by osteoarthritis. The aim of this study was twofold: to evaluate the pharmacokinetics and the pharmacodynamics of grapiprant in the induced inflammatory pain model in the rabbit after a single IV injection of 2 mg/kg; to compare the thermal antinociception effect after 2 mg/kg IV grapiprant, with that generated by 0.5 mg/kg meloxicam SC injected. Rabbits (n = 12) were randomly assigned to two crossover studies (single-dose, two-period crossover). The first study group A (n = 3) received a single IV dose of grapiprant at 2 mg/kg dissolved in ethanol. Group B (n = 3) received a single IV injection of ethanol (equivalent volume to grapiprant volume) at the same site. The second study group C (n = 3) received a single SC dose of meloxicam at 0.5 mg/kg. Group D (n = 3) received a single SC injection of 15% ethanol (equivalent volume to grapiprant volume) at the same site. After a 2-week washout period, the groups were rotated and the experiments repeated. Blood samples (0.7 mL) were collected from the right ear artery at assigned times and grapiprant plasma concentrations determined by a validated HPLC-FL method. Three hours prior to administration of the drugs, inflammation was induced by SC injection of lambda carrageenan (200 μL, 3% in physiological saline) under the plantar surface of the right hind paw. At a similar time to the blood collection, an infrared thermal stimuli (40 °C) was applied to the plantar surface of the rabbits' hindlimbs to evaluate the thermal withdrawal latency (TWL). The thermal antinociceptive effect was expressed as maximum possible response (% MPR). Grapiprant plasma concentrations were detectable up to the 10-h time point (concentration range 17-7495 ng/mL). The grapiprant-treated group showed a significant increase in TWL from 1 h and up to 10 h after drug administration compared to the control. In contrast, the meloxicam group showed a significant increase in TWL from 4 up to 10 h after drug administration, compared to control. The maximal MPR% was not statistically different between the grapiprant and meloxicam group from 4 to 8 h, while significant differences were shown at 1, 1.5, 2, 10 and 24 h. Given these findings, grapiprant appears to be an attractive option for antinociception in rabbits, due to its rapid onset and extended duration of effect.

Topics: Animals; Carrageenan; Cross-Over Studies; Disease Models, Animal; Dogs; Osteoarthritis; Pain; Rabbits; Random Allocation; Sulfonylurea Compounds; Treatment Outcome

Topics: Administration, Oral; Animals; Dogs; Dose-Response Relationship, Drug; Female; Inflammation; Male; Osteoarthritis; Pain; Receptors, Prostaglandin E, EP2 Subtype; Sulfonylurea Compounds; Suspensions; Tablets