Pharmacokinetics and penetration of danofloxacin from the blood into the milk of ewes.

The single-dose disposition kinetics of danofloxacin were determined in clinically normal, lactating ewes after intravenous (i.v.) and intramuscular (i.m.) administration of 1.25 mg/kg. The drug concentration in the blood serum and milk were determined by microbiological assay and the data were subjected to compartmental and non-compartmental kinetic analyses. The i.v. and im elimination half-lives in serum (t1/2 beta and t1/2el) were 125.0 +/- 38.6 min and 209.4 +/- 56.3 min, respectively. The steady-state volume of distribution (Vss) was 1.9 +/- 0.7 L/kg. The drug was quickly absorbed after the i.m. injection and the i.m. availability was 100%. Penetration of danofloxacin from the blood into the milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 60-90 min after administration and onwards. Milk danofloxacin concentrations equal to or higher than the minimal inhibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximately 24 h. Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.