Pharmacokinetics of dexamethasone with pharmacokinetic/pharmacodynamic model of the effect of dexamethasone on endogenous hydrocortisone and cortisone in the horse.

This study looked into how the drug Dexamethasone (DXM) affect concentrations of endogenous cortisone (COR) and hydrocortisone (HYD) in horses. Utilizing liquid chromatography interfaced with mass spectrometry, it was determined that levels of DXM significantly reduce the concentration of COR and HYD after one hour of DXM intravenous administration at a specific dose, with the chemicals returning to baseline levels after 96 hours.

Model and Methodology

• The researchers used a compartmental model to investigate the behavior of DXM along with its effects on endogenous cortisone and hydrocortisone in horses.
• This model was used to describe how the plasma levels of the dexamethasone, cortisone and hydrocortisone changed over time after intravenous injection of DXM at a dose of 0.05 mg/kg in horses.
• Quantification of these substances in the horses’ blood was achieved using liquid chromatography which was interfaced with a highly sensitive detection technique called triple spray quadrupole quantum tandem mass spectrometry (LC/TSQ-MS/MS).

Findings

• Timing of drug removal from the body was calculated by half-lives (α, β, γ) showing that the drug exits the system relatively quickly, with all horses showing levels below the quantification threshold 72 hours after drug administration.
• There were distinct drops in the baseline plasma concentrations of both COR and HYD one hour after DXM intravenous administration. The lowest concentration of cortisone was found after approximately 29 hours.
• However, plasma concentrations of both COR and HYD returned to baseline levels after 96 hours post-DXM administration, suggesting that DXM administration disrupts but does not permanently alter hormone levels.

Implications

• The sensitivity of the LC/TSQ-MS/MS allowed for a complete description of the pharmacokinetics of DXM and its impact on plasma concentrations of COR and HYD.
• This type of rigorous data-gathering and analysis facilitates a deeper understanding of how DXM operates in equine physiological systems at micro-levels.
• This could have implications for how veterinarians and pharmacologists administer and dose DXM in horses, as well as in further research on the impacts and benefits of DXM in equine medical treatments.