{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:21:00Z","timestamp":1789006860341,"version":"build-2803163510"},"reference-count":15,"publisher":"American Veterinary Medical Association (AVMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ajvr"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To investigate the safety of daily oral administration of grapiprant to dogs.<\/jats:p>\n<jats:p><jats:bold>ANIMALS<\/jats:bold> Thirty-six 9-month-old Beagles of both sexes.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> 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.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> 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.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> 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.<\/jats:p>","DOI":"10.2460\/ajvr.76.10.853","type":"journal-article","created":{"date-parts":[[2015,9,28]],"date-time":"2015-09-28T14:50:52Z","timestamp":1443451852000},"page":"853-859","source":"Crossref","is-referenced-by-count":43,"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"],"prefix":"10.2460","volume":"76","author":[{"given":"Lesley C.","family":"Rausch-Derra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margie","family":"Huebner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Rhodes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","series-title":"Review of the safety and efficacy of long-term NSAID use in the treatment of canine osteoarthritis","first-page":"226","volume":"166","author":"Innes","year":"2010"},{"key":"ref2","series-title":"Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs","first-page":"59","volume":"236","author":"Roush","year":"2010"},{"key":"ref3","series-title":"MF498 [N-{[4-(5,9-diethoxy-6-oxo-6,8-dihydro-7Hpyrrolo[3,4-g]quinolin-7-yl)-3-methylbenzyl]sulfonyl}-2-(2-methoxyphenyl)acetamide], a selective E prostanoid receptor 4 antagonist, relieves joint inflammation and pain in rodent models of rheumatoid and osteoarthritis","first-page":"425","volume":"325","author":"Clark","year":"2008"},{"key":"ref4","series-title":"Nonsteroidal anti-inflammatory drugs: a review","first-page":"298","volume":"41","author":"Curry","year":"2005"},{"key":"ref5","series-title":"Prostaglandin E2 receptor EP4 contributes to inflammatory pain hypersensitivity","first-page":"1096","volume":"319","author":"Lin","year":"2006"},{"key":"ref6","series-title":"The coxib NSAIDs: potential clinical and pharmacologic importance in veterinary medicine","first-page":"633","volume":"19","author":"Bergh","year":"2005"},{"key":"ref7","series-title":"Programme on International Nonproprietary Names (INN). Pre-stems: suffixes used in the selection of INN","year":"2013"},{"key":"ref8","series-title":"CJ-023,423, a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties","first-page":"686","volume":"322","author":"Nakao","year":"2007"},{"key":"ref9","series-title":"Standards for conduct of nonclinical studies on the safety of drugs","year":"1997"},{"key":"ref10","series-title":"OECD series on principles of good laboratory practice and compliance monitoring; consensus document of the Working Group on Good Laboratory Practices; No 13, application of the OECD Principles of GLP to the organization and management of multi-site studies","year":"2002"},{"key":"ref11","series-title":"SAS\/STAT 9.3 user's guide","year":"2011"},{"key":"ref12","series-title":"Clinical pharmacology of nonsteroidal anti-inflammatory drugs in dogs","first-page":"69","volume":"39","author":"KuKanich","year":"2012"},{"key":"ref13","series-title":"The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut","first-page":"883","volume":"109","author":"Kabashima","year":"2002"},{"key":"ref14","series-title":"Prostaglandin EP receptors involved in modulating gastrointestinal mucosal integrity","first-page":"248","volume":"114","author":"Takeuchi","year":"2010"},{"key":"ref15","series-title":"Arthritis in space and time\u2014to boldly go","first-page":"3640","volume":"585","author":"Benson","year":"2011"}],"container-title":["American Journal of Veterinary Research"],"original-title":[],"link":[{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/76\/10\/ajvr.76.10.853.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/76\/10\/ajvr.76.10.853.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/avmajournals.avma.org\/downloadpdf\/journals\/ajvr\/76\/10\/ajvr.76.10.853.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:36:34Z","timestamp":1741350994000},"score":1,"resource":{"primary":{"URL":"https:\/\/avmajournals.avma.org\/view\/journals\/ajvr\/76\/10\/ajvr.76.10.853.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,10]]},"references-count":15,"journal-issue":{"issue":"10"},"URL":"https:\/\/doi.org\/10.2460\/ajvr.76.10.853","relation":{},"ISSN":["0002-9645"],"issn-type":[{"value":"0002-9645","type":"print"}],"subject":[],"published":{"date-parts":[[2015,10]]}}}