PHARMACOKINETICS AND PENETRATION OF DANOFLOXACIN FROM THE BLOOD INTO THE MILK OF COWS

The single-dose disposition kinetics of danofloxacin were determined i n clinically normal lactating cows after intravenous (i.v.) and intram uscular (i.m.) administration of the drug at 1.25 mg/kg. The drug conc entrations in blood serum and milk were determined by microbiological assay methods and the data were subjected to kinetic analysis. The mea n i.v. and i.m. elimination half-lives (t(1/2el)) in serum were 54.9 a nd 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 b eginning 90-120 min after i.v. and i.m. administration and onwards. MI C) danofloxacin concentrations equal to or higher than the minimal inh ibitory concentrations (MIC) for pathogenic Gram-negative bacteria and Mycoplasma species were maintained over approximate to 24 h. Concentr ations greater than the MTC for Staphylococcus aureus were maintained in the milk for 12 h.