Pharmacokinetics of grapiprant and effects on TNF-alpha concentrations following oral administration to horses.

Autor: Hoffmann SL; K.L Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA., Seminoff K; K.L Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA., McKemie DS; K.L Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA., Kass PH; Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA., Knych HK; K.L Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
Jazyk: angličtina
Zdroj: Journal of veterinary pharmacology and therapeutics [J Vet Pharmacol Ther] 2022 Sep; Vol. 45 (5), pp. 467-472. Date of Electronic Publication: 2022 Jun 01.
DOI: 10.1111/jvp.13076
Abstrakt: Grapiprant is a prostaglandin E 2 receptor antagonist that has been found to be an effective anti-inflammatory in dogs and that is devoid of some of the adverse effects associated with traditional NSAIDs that elicit their effects through inhibition of PGE 2 production. Previously published reports have described the pharmacokinetics of this drug in horses when administered at 2 mg/kg; however, pharmacodynamic effects in this species have yet to be described. The objective of the current study was to describe the pharmacokinetics and pharmacodynamics of grapiprant at a higher dose. Eight horses received a single oral administration of 15 mg/kg. Plasma concentrations were determined for 96 h using liquid chromatography-tandem mass spectrometry. Non-compartmental analysis was used to determine pharmacokinetic parameters. Pharmacodynamic effects were assessed ex vivo by stimulating blood samples with PGE 2 and determining TNF-ɑ concentrations. Maximum concentration, time to maximum concentration and area under the curve were 327.5 (188.4-663.0) ng/ml, 1 (0.75-2.0) hour and 831.8 (512.6-1421.6) h*ng/ml, respectively. The terminal half-life was 11.1 (8.27-21.2) hr. Significant stimulation of TNF alpha was noted for 2-4 h post-drug administration. Results of this study suggest a short duration of EP4 receptor engagement when administered at a dose of 15 mg/kg.
(© 2022 John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: