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Pharmacology of grapiprant, a novel EP 4 antagonist: receptor binding, efficacy in a rodent postoperative pain model, and a dose estimation for controlling pain in dogs
Author(s) -
Nagahisa A.,
Okumura T.
Publication year - 2017
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12349
Subject(s) - medicine , osteoarthritis , inflammation , pharmacology , antagonist , analgesic , receptor , nociception , prostaglandin e2 , receptor antagonist , effective dose (radiation) , anesthesia , pathology , alternative medicine , radiology
Grapiprant is an analgesic and anti‐inflammatory drug in the piprant class that was approved in March 2016 by FDA 's Center for Veterinary Medicine for the control of pain and inflammation associated with osteoarthritis ( OA ) in dogs. Grapiprant functions as a selective antagonist of the EP 4 receptor, one of the four prostaglandin E 2 ( PGE 2 ) receptor subtypes. The EP 4 receptor mediates PGE 2 ‐elicited nociception, and grapiprant has been shown to decrease pain in several rat inflammatory pain models. It was also effective in reducing pain associated with OA in humans, providing evidence for its mechanism of action in these species. The estimated canine efficacy dose of between 1.3 and 1.7 mg/kg, p.o. with a methylcellulose suspension, once a day, was predicted based on calculations from comparative affinity of grapiprant to the dog, rat, and human EP 4 receptors, serum protein binding, effective doses defined in rat models of pain and inflammation, and human clinical studies. The results of this study guided the doses to be tested in the pilot study and demonstrated the usefulness of the efficacy dose prediction method. The approved commercial tablet dose of grapiprant is 2 mg/kg once a day for the control of pain and inflammation associated with OA in dogs.