Pharmacokinetics and penetration of danofloxacin from the blood into the milk of cows

The single-dose disposition kinetics of danofloxacin were determined in clinically normal lactating cows after intravenous (i.v.) and intramuscular (i.m.) administration of the drug at 1.25 mg/kg. The drug concentrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mean i.v. and i.m. elimination half-lives (t( 1/4 el)) in serum were 54.9 and 135.7 min, respectively. The steady-state volume of distribution (V(ss)) was 2.04 L/kg. The drug was quickly absorbed after i.m. injection but a 'flip flop' effect was clearly evident and bioavailability was > 100%. Penetration of danofloxacin from blood into milk was rapid and extensive with drug concentrations in milk exceeding those in serum beginning 90-120 min after i.v. and i.m. 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 ≃ 24 h. Concentrations greater than the MIC for Staphylococcus aureus were maintained in the milk for 12 h.