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Vétoquinol, R&D Department, B.P. 189, 70204 Lure, France
Corresponding author: M. Schneider; e-mail: marc.Schneider{at}vetoquinol.com.
The plasma and milk pharmacokinetics of marbofloxacin, a fluoroquinolone antibacterial compound, were evaluated in dairy cows, as well as its pharmacodynamic characteristics against mastitis-isolated pathogens. Marbofloxacin was given intramuscularly as a 10% aqueous solution to dairy cows either at a single dose or at repeated doses of 2 mg/kg once daily for 3 d. Blood and milk samples were collected for the determination of the concentration of marbofloxacin and of its putative metabolites: N-desmethyl-marbofloxacin and N-oxide-marbofloxacin. Bacterial field isolates were from milk samples collected from dairy cows suspected of having an intramammary infection. After identification, the minimal inhibitory concentration (MIC) was determined against the isolated strains. The maximal marbofloxacin concentration (Cmax) observed in milk after the first administration was 1.024 µg/mL, and the area under the curve during the first dosing interval was 6.513 µg/h per milliliter. After the third administration, these parameters were slightly increased (about 20% at most). Both metabolites were detected in the milk, but their concentrations were below the limit of quantification. The MIC against 90% of the population (MIC90) of Escherichia coli was 0.016 µg/mL, and it was 0.229 µg/mL against Staphylococcus aureus. The following surrogate clinical outcome markers were obtained against E. coli strains: a Cmax/MIC ratio of 67 and an area under the curve/MIC ratio of 407 h. Hence, a possible efficacy of marbofloxacin in the treatment of E. coli-induced mastitis could be expected as the endpoints of 10 and 250 h, respectively, are reached.
Key Words: marbofloxacin • pharmacokinetics • pharmacodynamics • surrogate marker
Abbreviation key: AUC = area under the curve, AUClast = area under the concentration-time curve until the last measurable time point, Cmax = maximum concentration, Cmax 1stobs = Cmax observed after the first administration, Cmax3rdobs = Cmax observed after the third administration, LOQ = limit of quantification, MBC = minimum bactericidal concentration, MIC = minimum inhibitory concentration, MIC50 = concentration of antibiotic able to inhibit the visible growth of 50% of a population of microorganisms, MIC90 = concentration of antibiotic able to inhibit the visible growth of 90% of a population of microorganisms, MRTlast = mean residence time till the last measurable time point, Tmax = occurrence time of the maximum plasma concentration, T
K01 = absorption half-life, T
z1st = elimination half-life after the first administration, Tz3rd = elimination half-life after the third administration
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