Determination of grapiprant plasma and urine concentrations in horses

Objective Non-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E-2 receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma. Study design Experimental study. Animals A total of six healthy, adult mixed-breed mares weighing 502 +/- 66 (397-600) kg and aged 14.8 +/- 5.3 (6-21) years. Methods Mares were administered one dose of 2 mg kg(-1) grapiprant via nasogastric tube. Blood and urine samples were collected prior to and up to 48 hours after drug administration. Drug concentrations were measured using high-performance liquid chromatography. Results Grapiprant plasma concentrations ranged from 71 to 149 ng mL(-1) with the mean peak concentration (106 ng mL(-1)) occurring at 30 minutes. Concentrations were below the lower limit of quantification (50 ng mL(-1)) in four of six horses at 1 hour and in all six horses by 2 hours after drug administration. Grapiprant urine concentrations ranged from 40 to 4077 ng mL(-1) and were still detectable at 48 hours after administration. Conclusions and clinical relevance Currently, there are no published studies looking at the pharmacodynamics of grapiprant in horses. The effective concentration needed to control pain in dogs ranges 114-164 ng mL(-1). Oral administration of grapiprant (2 mg kg(-1)) in horses did not achieve those concentrations. The dose was well tolerated; therefore, studies with larger doses could be conducted.