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Detection and pharmacokinetics of three formulations of firocoxib following multiple administrations to horses
Author(s) -
Knych H. K.,
Stanley S. D.,
Arthur R. M.,
Mitchell M. M.
Publication year - 2014
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12211
Subject(s) - horse , pharmacokinetics , crossover study , plasma concentration , medicine , zoology , half life , chemistry , pharmacology , biology , paleontology , alternative medicine , pathology , placebo
Summary Reason for performing study The use of firocoxib in horses and its ability to affect performance and potential to allow a horse to compete when it otherwise should not, necessitates establishing appropriate withdrawal time guidelines prior to performance. Objectives To describe plasma concentrations and characterise the pharmacokinetics of 3 firocoxib formulations following multiple administrations of the label dose, with respect to recommended plasma thresholds for performance horses. Study design Balanced 3‐way crossover prospective study. Methods Nine healthy mature horses were administered firocoxib injectable solution (0.09 mg/kg bwt i.v. s.i.d. for 5 days), firocoxib paste (0.1 mg/kg bwt per os s.i.d. for 14 days) and firocoxib tablets (57 mg s.i.d. for 14 days). Blood samples were collected at Time 0 and at various times post drug administration until plasma concentrations were below the limit of detection of the assay. Plasma samples were analysed using liquid chromatography‐mass spectrometry and data analysed using noncompartmental analysis. Results The mean plasma half‐life was 1.64 ± 0.737, 1.70 ± 0.800 and 1.73 ± 0.767 days for injectable, paste and tablet formulations, respectively. Plasma concentrations fell below the R acing M edication and T esting C onsortium's recommended threshold for racehorses (20 ng/ml) by 7 days post administration of the final dose for all formulations. Plasma concentrations never exceeded the threshold concentration (240 ng/ml) for horse competing in US E questrian F ederation events for any of the formulations. Conclusions This study extends current knowledge regarding the pharmacokinetics of firocoxib and provides information that can be used to establish appropriate withdrawal time guidelines following multiple administrations, with respect to already established plasma regulatory threshold concentrations.