title: The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses.
abstract: The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half-life (t(1/2) k(10) ) of 12.49 ± 1.84 h. The average maximum plasma concentration (C(max) ) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX-2 with a COX-1/COX-2 ratio of 25.67 and 22.06 for the IC(50) and IC(80) , respectively. Dosing simulations showed that concentrations above the IC(80) for COX-2 would be maintained following 2 mg/kg PO q12h, and above the IC(50) following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti-inflammatory treatment of various conditions in the horse.
authors.affiliation: Department of Clinical Sciences Department of Molecular and Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, NC 27606, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Davis
authors.forename: J F
authors.initials: JF
authors.lastname: Marshall
authors.forename: M G
authors.initials: MG
authors.lastname: Papich
authors.forename: A T
authors.initials: AT
authors.lastname: Blikslager
authors.forename: N B
authors.initials: NB
authors.lastname: Campbell
mesh_terms: D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006736:Horses / Q000097:blood* / Q000378:metabolism; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D016861:Cyclooxygenase Inhibitors; D013449:Sulfonamides; C471996:deracoxib; D000096926:Benzenesulfonamides