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Background: Flumetasone is a potent corticosteroid reportedly used in horses to decrease inflammation associated with strenuous exercise. There are currently no reports describing the use of this drug in horses., Objectives: To describe the pharmacokinetics and effects on cortisol and eicosanoid concentrations, following administration of flumetasone to exercised horses., Study Design: Parallel design., Methods: Twelve exercised horses received a single i.v. administration of 5 mg of flumetasone. Blood and urine samples were collected before and for 72 h post-drug administration for determination of flumetasone and cortisol concentrations. Whole blood samples were collected at various time and challenged with lipopolysaccharide, calcium ionophore or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flumetasone, cortisol and eicosanoids were measured using LC-MS/MS and pharmacokinetic/pharmacodynamic analysis performed., Results: Flumetasone was detected for 23.5 ± 1.73 h in blood. The volume of distribution at steady state, systemic clearance and elimination half-life was 5.90 ± 0.200 L/kg, 30.7 ± 0.166 mL/min/kg and 4.84 ± 0.83 h respectively. Cortisol concentrations were still suppressed at last time point collected (72 h). For cortisol, K in , K out and the t 1/2out were 30.3 ± 1.56 ng/mL × h, 0.331 ± 0.02 1/h and 2.1 h respectively. Stimulation with lipopolysaccharide resulted in a decrease in TXB 2 , PGF 2 , LTB 4 , 15-HETE and 5-HETE for up to 72 h and PGE 2 for 24 h post-flumetasone administration. Stimulation of whole blood with calcium ionophore resulted in a decrease in LTB 4 for up to 6 h and 15-HETE at 8 h., Main Limitations: Lack of sample collection for determination of biomarker concentrations beyond 72 h and the use of a single sample for determination of baseline cortisol concentrations., Conclusions: Flumetasone is rapidly cleared from blood following administration to horses. It is a potent anti-inflammatory with prolonged effects on production of cortisol and other inflammatory mediators., (© 2018 EVJ Ltd.)