title: Evaluation of the safety of long-term, daily oral administration of grapiprant, a novel drug for treatment of osteoarthritic pain and inflammation, in healthy dogs.
abstract: OBJECTIVE
  To investigate the safety of daily oral administration of grapiprant to dogs.
  
  
  METHODS
  Thirty-six 9-month-old Beagles of both sexes.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Rausch-Derra
authors.forename: Margie
authors.initials: M
authors.lastname: Huebner
authors.forename: Linda
authors.initials: L
authors.lastname: Rhodes
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004283:Dog Diseases / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D005260:Female; D008297:Male; D010003:Osteoarthritis / Q000188:drug therapy / Q000662:veterinary*; D010147:Pain Measurement / Q000662:veterinary; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D007093:Imidazoles; D011725:Pyridines; D000096926:Benzenesulfonamides
chemical_list: D016861:Cyclooxygenase Inhibitors; D013453:Sulfonylurea Compounds; C522837:grapiprant; D007093:Imidazoles; D011725:Pyridines; D000096926:Benzenesulfonamides