Pharmacokinetics of intravenous flumetasone and effects on plasma hydrocortisone concentrations and inflammatory mediators in the horse.
Authors: Knych H K, Arthur R M, McKemie D S, Baden R, Oldberg N, Kass P H
Journal: Equine veterinary journal
Summary
# Pharmacokinetics of Intravenous Flumetasone in Horses Flumetasone, a potent corticosteroid sometimes used in equine practice to manage post-exercise inflammation, had never been formally characterised in horses until this 2019 study. Knych and colleagues administered a single 5 mg intravenous dose to twelve exercised horses, then tracked flumetasone concentrations, cortisol suppression, and inflammatory mediator production (eicosanoids) using liquid chromatography-mass spectrometry across a 72-hour period. The drug cleared rapidly from circulation with an elimination half-life of approximately 4.8 hours, yet cortisol remained suppressed throughout the entire 72-hour observation window, with an estimated suppression half-life of 2.1 hours—indicating prolonged hypothalamic-pituitary-adrenal axis inhibition. Ex vivo challenges with lipopolysaccharide showed dramatic reductions in multiple eicosanoid markers (thromboxane B2, prostaglandin F2α, leukotriene B4, and hydroxyeicosatetraenoic acids) persisting for up to 72 hours, though the clinical significance of suppressing these inflammatory mediators in exercised horses warrants further investigation. This pharmacodynamic profile suggests flumetasone produces sustained anti-inflammatory effects well beyond its detectability in plasma, a consideration for practitioners using this agent in competition horses and those subject to doping controls, particularly given the persistent cortisol suppression observed.
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Practical Takeaways
- •Flumetasone provides prolonged anti-inflammatory effects lasting at least 72 hours despite rapid blood clearance, making it potentially useful for managing post-exercise inflammation in horses
- •The drug's profound suppression of cortisol for 72+ hours should be considered when assessing adrenal function or using multiple corticosteroid doses in clinical practice
- •Practitioners should note that flumetasone's anti-inflammatory effects extend beyond its detectable presence in blood, suggesting sustained pharmacodynamic activity
Key Findings
- •Flumetasone is rapidly cleared from blood with an elimination half-life of 4.84 ± 0.83 hours and was detected for 23.5 ± 1.73 hours post-administration
- •Cortisol concentrations remained suppressed for at least 72 hours following a single 5 mg intravenous dose of flumetasone
- •Flumetasone demonstrated potent anti-inflammatory effects with decreased eicosanoid production (TXB2, PGF2α, LTB4, 15-HETE, 5-HETE) for up to 72 hours following lipopolysaccharide stimulation
- •The volume of distribution at steady state was 5.90 ± 0.200 L/kg with systemic clearance of 30.7 ± 0.166 mL/min/kg