Pharmacokinetics of grapiprant in goat kids at two different dosing regimens

Abstract

Most non-steroidal anti-inflammatory drugs (NSAIDs) used in large animals have significant potential for adverse effects via inhibition of cyclooxygenase enzymes, such as gastric ulceration and nephrotoxicity. A new class of anti-inflammatory medications, the priprant class, act via inhibition of the P4 receptor of prostaglandin E2 and have no effect on cyclooxygenase enzymes potentially giving them a wider safety margin. Grapiprant is a medication currently labeled for the treatment of osteoarthritis in dogs and no research is available regarding its pharmacokinetics and pharmacodynamics parameters in small ruminants. To assess this, six cross bred goat kids were orally administered either 2 mg/kg or 4 mg/kg grapiprant (via a bottle with the tablets crushed in the milk) and blood samples were collected. Plasma samples underwent UPLC analysis. A non-compartmental analysis was performed to determine pharmacokinetic parameters. Wilcoxon’s ranked sum test was utilized to compare the two dosing groups for specific pharmacokinetic parameters (Cmax, Tmax, AUC0-∞, T1/2λ, CL/F and Vd/F). During the study, there were no adverse effects noted. For goat kids administered 2 mg/kg orally, the geometric mean for peak concentration is 203.35 ng/mL. For the goat kids administered 4 mg/kg orally, the geometric mean for peak concentration is 294.22 ng/mL. The results of this study demonstrate that plasma concentrations reached levels that have been shown to improve pain scores in rats and dogs and future studies are needed to assess its efficacy as an analgesic in ruminant species.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.