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Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses
Author(s) -
Holland B.,
Fogle C.,
Blikslager A. T.,
Curling A.,
Barlow B. M.,
Schirmer J.,
Davis J. L.
Publication year - 2015
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12177
Subject(s) - pharmacokinetics , bioequivalence , bioavailability , pharmacodynamics , crossover study , pharmacology , medicine , volume of distribution , oral administration , oral dose , withdrawal time , horse , placebo , paleontology , alternative medicine , colorectal cancer , colonoscopy , pathology , cancer , biology
The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three‐way, randomized, crossover design. Blood was collected at predetermined times for PGE 2 and TXB 2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half‐life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher C max , shorter T max , and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE 2 was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC 50 of approximately 27 ng/mL and an IC 80 of 108 ng/ mL for COX2 inhibition. Inhibition of TXB 2 production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.