Pharmacokinetics of grapiprant, a selective EP₄ prostaglandin PGE₂ receptor antagonist, after 2 mg/kg oral and i.v. administrations in cats

Abstract

Drugs that provide effective analgesia in cats are limited. The aim of the study was to assess the pharmacokinetics of grapiprant after 2 mg/kg administration via p.o. and i.v. routes in cats. Six healthy adult cats were used according to an open, single-dose, two-treatment, two-period, randomized cross-over design. Cats were assigned to two treatment groups and administered with 2 mg/kg of grapiprant (pure powder) through p.o. and i.v. administration. Blood samples were collected at preassigned times and analysed by a validated HPLC method. After both administrations, grapiprant concentrations were detectable in plasma for up to 24 hr in five of six animals. The critical parameters including clearance (173.2 ml hr kg , range 120-326 ml hr kg ) and volume of distribution (918 ml/kg, range 611-1608 ml/kg) were calculated from the i.v. group. The mean oral F% was low (39.6% range 31.5%-45.2%). If the assumption that the minimal effective concentration in dogs (164 ng/ml) applies in cats too, grapiprant orally administered at 2 mg/kg might be effective for 10 hr. Further studies are necessary to establish the minimal effective concentration in this animal species.

Detection and pharmacokinetics of grapiprant following oral administration to exercised Thoroughbred horses

“…The elimination half‐life reported for dogs range from 2.99 to 9.12 hours following a single oral administration while in cats, it is 1.42–6.05 hours . In the current study, the elimination half‐life for horses was slightly longer, ranging from 4.06 to 11.1 hours.…”

“…Based on this, in the current study, food was withheld for 4 hours following grapiprant administration. The time to maximum concentration was similar between dogs (1–2 hours), cats (1.33 hours), and horses (0.5–2 hours).…”

“…While the pharmacokinetics of grapiprant have been described in other species, to the best of the authors' knowledge there no reports in horses. In the current study, the C max ranged from 5.93 to 56.3 ng/mL following oral administration of a 2 mg/kg dose.…”

“…This is much lower than what has been reported for other species following administration of an equivalent dose. In cats, C max is reportedly 490–750 ng/mL . Maximal plasma concentrations were 1598 ng/mL in fasted and 614 ng/mL in fed dogs following administration of an oral dose of 2 mg/kg .…”

“…Rausch‐Derra et al reported that grapiprant is an effective treatment for alleviation of pain in dogs with osteoarthritis and appears to be better tolerated than other treatments following administration of 2 mg/kg daily for 28 days . Although not approved for use in cats, investigators have also reported that grapiprant is well tolerated when administered at doses of 3, 9, and 15 mg/kg daily for 28 days to this species . To the best of our knowledge, there are no reports in the literature describing the use of grapiprant in horses; however, if this drug proves to be effective and safe, it may provide veterinarians with an additional therapeutic option for the treatment of inflammation in horses.…”