Pharmacokinetics and milk penetration of difloxacin after a long-acting formulation for subcutaneous administration to lactating goats

The single-dose disposition kinetics of difloxacin were determined in clinically normal lactating goats (n = 6) after intravenous (IV) and subcutaneous (SC) administration and subcutaneous administration of a long-acting poloxamer 407 gel formulation (P407). Difloxacin concentrations were determined by HPLC with fluorescence detection. Minimum inhibitory concentrations of difloxacin against 14 strains of Staphylococcus aureus isolated from mastitic goats' milk in Spain were determined to compute pharmacodynamic surrogate markers. The concentration-time data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Following SC and P407 administration, difloxacin achieved maximum milk concentrations of 1.34 ± 0.12 and 2.97 ± 1.18 mg/L, respectively, at 4.00 ± 0.00 h (SC) and 3.60 ± 0.89 h (P407) after administration. The absolute bioavailabilities after SC and P407 administration were 81.74 ± 15.60% and 72.58 ± 20.45%, respectively. Difloxacin penetration from the blood into the milk was good and high concentrations were found in milk secretions. From these data, a 15 mg/kg dose of difloxacin P407 would appear to be effective against Staphylococcus aureus isolated from mastitic goats' milk with minimum inhibitory concentrations ≤0.25 mg/L.