Bioavailability and tolerability of nebulised dexamethasone sodium phosphate in adult horses.

The research is about the administration of Dexamethasone Sodium Phosphate (DSP) to horses using nebulisation as an affordable way to target asthma. It checks if this method shows minimal systemic absorption, doesn’t cause airway inflammation, and evaluates its bioavailability.

Research Overview

In this study, the researchers investigated the bioavailability and safety of nebulised DSP in adult horses. Nebulisation of a potent corticosteroid like DSP is seen as a cost-effective method of direct delivery into horses’ lungs, especially those suffering from asthma. However, the success of this method is contingent on minimal systemic absorption and the non-induction of airway inflammation due to the preservatives used in DSP.

Methodology

The study involved six healthy adult horses and followed a randomised crossover experiment design. The researchers administered DSP to the horses in two separate ways:

• Through nebulisation: DSP was nebulised and administered at a dose of 5 mg every 24 hours for five days
• Through intravenous (i.v.) injection: DSP was injected intravenously following the same dosage and frequency

They then measured the plasma dexamethasone concentrations using UPLC/MS-MS to calculate the drug’s bioavailability. In addition, cytological examinations of bronchoalveolar fluid were performed before the start of DSP administration and after the last dose. Furthermore, a validated chemiluminescent immunoassay was utilised to measure basal serum cortisol concentrations.

Results

Following nebulisation, Dexamethasone showcased a mean maximum plasma concentration of 0.774 ± 0.215 ng/mL and a systemic bioavailability of 4.3 ± 1.2%. Interestingly, irrespective of the route of DSP administration, the percentage of neutrophils in bronchoalveolar lavage fluid significantly decreased over time. During intravenous administration, the basal serum cortisol concentration decreased significantly from baseline to Day 3 and remained low on Day 5. In contrast, the basal serum cortisol concentration did not change significantly during administration via nebulisation.

Conclusion

The study’s conclusion was based on a small sample size and a short period of DSP administration. However, the results suggested that Dexamethasone Sodium Phosphate administration via nebulisation presented minimal systemic bioavailability and did not induce lower airway inflammation or suppression of the hypothalamic-pituitary-adrenal (HPA) axis in the healthy horses tested. This could represent a scalable treatment option for horses with asthma, with further study needed to confirm efficacy on horses with respiratory disorders.