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

Abstract

Traditional therapeutic options for the treatment of lameness associated with inflammation in performance horses include administration of cyclooxygenase enzyme inhibiting non-steroidal anti-inflammatory drugs (NSAID). As long-term use of these drugs can adversely impact the health of the horse, anti-inflammatories with a more favorable safety profile are warranted. Grapiprant is a newly approved non-cyclooxygenase inhibiting NSAID that has demonstrated efficacy and safety in other species and which may be a valuable alternative to traditional NSAIDs used in the horse. The objectives of the current study were to describe drug concentrations and the pharmacokinetics of grapiprant in exercised Thoroughbred horses and to develop an analytical method that could be used to regulate its use in performance horses. To that end, grapiprant, at a dose of 2 mg/kg was administered orally to 12 exercised Thoroughbred horses. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Drug concentrations were measured using liquid chromatography-tandem mass spectrometry. Grapiprant remained above the LOQ of the assay (0.005 ng/mL) in serum for 72 hours post administration and urine concentrations were above the LOQ until 96 hours. The C , T and elimination half-life were 31.9 ± 13.9 ng/mL, 1.5 ± 0.5 hours and 5.86 ± 2.46 hours, respectively. The drug was well tolerated in all horses at a dose of 2 mg/kg. Results support further study of this compound in horses. Furthermore, development of a highly sensitive analytical method demonstrate that this compound can be adequately regulated in performance horses.

Grapiprant: A snapshot of the current knowledge

“…A number of analytical methods for the quantification of grapiprant in different biological matrices have been published (Baralla et al, 2018 ; Cox et al, 2020 ; De Vito et al, 2016 , 2017 ; Heit et al, 2018 ; Knych et al, 2018 ; Łebkowska‐Wieruszewska et al, 2017 ; Nagahisa & Okumura, 2017 ). The devices used for the quantification of grapiprant are HPLC and LC‐MS/MS.…”

“…The drug concentrations and the pharmacokinetics of grapiprant in exercised Thoroughbred horses administered with a 2 mg/kg oral dose of grapiprant were described (Knych et al, 2018 ).…”

“…Rabbits after single IV (0.5 mg/kg) and PO (2 mg/kg) dose and horses after single PO dose (2 mg/kg) did not report any significant adverse effects (Cox et al, 2020 ; De Vito et al, 2017 ; Knych et al, 2018 ).…”

Non‐steroidal anti‐inflammatory drugs in equine orthopaedics

“…Blood and urinary samples collected from these dogs during the study period remained within the reference intervals. Two studies have been performed evaluating the pharmacokinetics of grapiprant in horses 83,84 . When grapiprant was administered to horses orally at the therapeutic dose for dogs (2 mg/kg), the drug was well tolerated; however, the effective concentration required for pain control in dogs was not achieved in horses 83 .…”

“…Two studies have been performed evaluating the pharmacokinetics of grapiprant in horses. 83 , 84 When grapiprant was administered to horses orally at the therapeutic dose for dogs (2 mg/kg), the drug was well tolerated; however, the effective concentration required for pain control in dogs was not achieved in horses. 83 Based on these studies, there is no clinical evidence currently that grapiprant could be an alternate to NSAID administration in horses.…”