# Influence of Dexamethasone on the Plasma and Milk Disposition Kinetics of Danofloxacin in Lactating Sheep

## TL;DR

This study shows that dexamethasone increases danofloxacin levels in sheep's milk, which could affect drug safety and milk quality.

## Contribution

The study reveals that dexamethasone significantly increases danofloxacin concentrations in sheep milk without affecting plasma levels.

## Key findings

- Dexamethasone did not alter plasma disposition of danofloxacin.
- High-dose dexamethasone significantly increased danofloxacin concentrations in sheep milk.
- Milk-to-plasma AUC ratio of danofloxacin increased with dexamethasone treatment.

## Abstract

This study examines the effects of different doses of dexamethasone on the behavior of danofloxacin in the plasma and milk of lactating sheep. Understanding this interaction is crucial as both drugs are frequently used in veterinary medicine and may influence therapeutic effectiveness and milk safety. The research involved six lactating ewes, with plasma and milk samples collected at various intervals after administering low and high doses of dexamethasone alongside danofloxacin. The results revealed that although dexamethasone did not alter danofloxacin disposition in the plasma, it significantly increased its concentration in the milk, particularly at higher doses. This raises important concerns for both therapeutic efficacy and milk safety, as it indicates that milk from sheep treated with dexamethasone could contain higher danofloxacin concentrations. Overall, the findings underscore the need for careful evaluation of these medications’ combined use to ensure both optimal treatment outcomes for animals and the safety of milk products for consumers.

This study planned to evaluate the impact of low (0.1 mg/kg) and high (1 mg/kg) doses of dexamethasone on the plasma and milk distribution of danofloxacin (6 mg/kg) in sheep after intravenous administration. Utilizing a crossover pharmacokinetic design, the research was conducted on six lactating ewes, with blood and milk samples collected at 18 predetermined time points over a 48-h period. Danofloxacin analysis from plasma and milk samples was performed by high-performance liquid chromatography. The pharmacokinetic data were derived using non-compartmental analysis. Plasma t1/2ʎz, AUC0–∞, ClT, and Vdss values of danofloxacin were found to be 5.20 h, 9.26 h*µg/mL, 0.65 L/h/kg, and 4.23 L/kg, respectively. The administration of both low and high doses of dexamethasone did not result in any changes in the plasma pharmacokinetics of danofloxacin. Milk t1/2ʎz, AUC0–∞, and Cmax values of danofloxacin were 4.30 h, 99.52 h*µg/mL, and 20.61 µg/mL, respectively. Dexamethasone administration resulted in prolonged milk t1/2ʎz, with high-dose dexamethasone significantly enhancing both the milk AUC0–∞ and Cmax of danofloxacin. The AUC0–∞ milk/AUC0–∞ plasma ratio of danofloxacin was 10.75 and was further increased with dexamethasone treatment. These results highlight the necessity for careful evaluation of drug interactions in lactating sheep to ensure both efficacy and safety, as well as the need for further research to establish guidelines for concurrent administration of dexamethasone and danofloxacin.