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

The single-dose disposition kinetics of danofloxacin were determined i n clinically normal, lactating ewes after intravenous (iv) and intramu scular (im) administration of 1.25 mg/kg. The drug concentration in th e blood serum and milk were determined by microbiological assay and th e data were subjected to compartmental and non-compartmental kinetic a nalyses. The iv and im elimination half-lives in serum (t(1/2 beta) an d t(1/2el)) were 125.0 +/- 38.6 min and 209.4 +/- 56.3 min, respective ly. The steady-state volume of distribution (V-SS) was 1.9 +/- 0.7 L/k g. The drug was quickly absorbed after the im injection and the im ava ilability was 100%. Penetration of danofloxacin from the blood into th e milk was rapid and extensive with drug concentrations in milk exceed ing those in serum beginning 60-90 min after administration and onward s. Milk danofloxacin concentrations equal to or higher than the minima l inhibitory concentrations (MIC) for pathogenic Gram-negative bacteri a and Mycoplasma species were maintained over approximately 24 h. Conc entrations greater than the MIC for Staphylococcus aureus were maintai ned in the milk for 12 h.