Pharmacokinetics and penetration of marbofloxacin from blood into the milk of cows and ewes.

The single-dose disposition kinetics of marbofloxacin were determined in lactating cows and ewes after intravenous (i.v.) and intramuscular (i.m.) administration of 2, 2.5 and 4 mg/kg. Drug concentrations in blood and milk were determined by microbiological assay and the data were subjected to compartmental and non-compartmental kinetic analyses. In cows, the i.v. serum elimination half-life (t1/2 beta) was approximately 2 h and the i.m. serum elimination half-life (t1/2el) was approximately 3 h. The mean steady-state volume of distribution (Vss) was 1.5 l/kg for the cows and 0.6 l/kg for the ewes. The i.m. availability was nearly 100% for both cows and ewes. Drug penetration into the milk was rapid and extensive with milk marbofloxacin concentrations exceeding those in serum 2 h after administration. Milk drug concentrations equal to or greater than the minimal inhibitory concentrations for the majority of gram-negative udder pathogens were maintained for approximately 12 h after i.v. and i.m. treatment of 2-4 mg/kg. The drug was not detected in milk 24 h after treatment (sensitivity limit of assay = 0.05 microgram/ml).