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

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 t_1/2ʎz, AUC_0-∞, Cl_T, and V_dss 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 t_1/2ʎz, AUC_0-∞, and C_max values of danofloxacin were 4.30 h, 99.52 h*µg/mL, and 20.61 µg/mL, respectively. Dexamethasone administration resulted in prolonged milk t_1/2ʎz, with high-dose dexamethasone significantly enhancing both the milk AUC_0-∞ and C_max of danofloxacin. The AUC_{0-∞ milk}/AUC_{0-∞ 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.