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

J Vet Pharmacol Ther. 2017 Dec;40(6):e11-e15. doi: 10.1111/jvp.12414. Epub 2017 Apr 29.

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-1 kg-1 , range 120-326 ml hr-1 kg-1 ) 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.

Keywords: EP4 receptor antagonist; bioavailability; cats; grapiprant; pharmacokinetics.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Animals
  • Cats
  • Cross-Over Studies
  • Injections, Intravenous / veterinary
  • Male
  • Receptors, Prostaglandin E, EP4 Subtype / antagonists & inhibitors*
  • Sulfonylurea Compounds / administration & dosage
  • Sulfonylurea Compounds / blood
  • Sulfonylurea Compounds / pharmacokinetics*

Substances

  • Receptors, Prostaglandin E, EP4 Subtype
  • Sulfonylurea Compounds
  • grapiprant