Pharmacokinetics of intravenous flumetasone and effects on plasma hydrocortisone concentrations and inflammatory mediators in the horse.

The research investigates the pharmacokinetics of flumetasone, a potent corticosteroid, in horses. It further examines the drug’s effects on cortisol and eicosanoid concentrations.

Research Methodology

• The study utilized a parallel design in which twelve exercised horses were given a single intravenous (i.v.) dose of 5mg flumetasone.
• Blood and urine samples were taken before and intermittently for 72 hours post-drug administration. These samples were used to measure concentrations of flumetasone and cortisol.
• Through ex vivo synthesis, eicosanoid concentrations were determined. This process involved challenging whole blood samples, collected at various times, with lipopolysaccharide, calcium ionophore, or methanol.
• All measurements were carried out using Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) and pharmacokinetic/pharmacodynamic analysis.

Research Findings

• The presence of flumetasone in the blood was observed for 23.5 ± 1.73 hours. This implicates the rapid clearance of the drug in the blood of horses.
• Key parameters for flumetasone were: volume of distribution at steady-state (5.90 ± 0.200 L/kg), systemic clearance (30.7 ± 0.166 mL/min/kg), and elimination half-life (4.84 ± 0.83 hours).
• Cortisol levels were observed to be suppressed up to the last collection point, 72 hours post-administration of the flumetasone.
• Parameters for cortisol were also determined: K (30.3 ± 1.56 ng/mL × h), K (0.331 ± 0.02 1/h), and the t (2.1 hours).
• The administration of flumetasone resulted in declines in specific eicosanoids, namely TXB, PGF, LTB, 15-HETE, and 5-HETE, up to 72 hours. It also influence the decrease in PGE up to 24 hours.

Conclusions

• The constraints of the study included the limitation of biomarker concentration determination past 72 hours and the use of a single sample for determining baseline cortisol concentrations.
• Despite these limitations, the use of flumetasone demonstrated rapid clearance from the blood once administered to the horses.
• It was also identified that flumetasone has a strong anti-inflammatory effect with extended effects on the production of cortisol and other inflammatory mediators.