Pharmacokinetics of Marbofloxacin in Lactating Cows After Repeated Intramuscular Administrations and Pharmacodynamics Against Mastitis Isolated Strains

Abstract

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 microg/mL, and the area under the curve during the first dosing interval was 6.513 microg/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 microg/mL, and it was 0.229 microg/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.

Integration of Pharmacokinetic and Pharmacodynamic Indices of Marbofloxacin in Turkeys

“…It has a broad spectrum of activity (58), and bactericidal concentration-dependent killing is observed against many gram-negative bacteria (12,49,51,52). The pharmacokinetic (PK) properties of marbofloxacin have been studied in several mammalian species, and some advantages over other fluoroquinolones, such as a longer elimination half-life, have been described (2,43,47,48). In practice, this would enable a single treatment per 24 h, with serum concentrations remaining above the MIC for more than 12 h. Comparable kinetic data for turkeys are lacking, however, as yet.…”

“…Hence, this approach determines ex vivo PK-PD indices, which subsequently allow a more targeted design in confirmatory in vivo studies (1,2,3). PK-PD experiments with marbofloxacin were previously conducted with calves, cows, goats, and dogs (2,43,48,55). Moreover, pharmacokinetic data for marbofloxacin have been estimated for chickens and Eurasian buzzards (6,20).…”

Pharmacokinetics of Marbofloxacin Following Single and Repeated Dose Intravenous Administration in Broiler Chickens

“…Whereas, lower values of t 1/2β were found (1.47 ± 0.31 h) in ostriches (De Lucas et al, 2005), (2.83 ± 0.28 h) Muscovy ducks (Goudah and Hasabelnaby, 2010), and (4.03 ± 0.08 h) Japanese quails (Aboubakr and Abdelazem, 2015). In contrast to this, Schneider et al, (2004) observed little high value of t 1/2β of 6.27  2.80 h, after repeated i.m. administration of marbofloxacin (2 mg/kg, for 3 days) in lactating cows.…”

Determination of Marbofloxacin residues in Rabbit Tissues by HPLC

“…Marbofloxacin is a third generation of fluoroquinolone with broad spectrum antimicrobial activity against some grampositive, most gram-negative organisms and Mycoplasma [2][3][4] with a relatively low concentration [5,6]. It prevents the bacterial DNA replication and synthesis via inhibition of the A subunit of the bacterial DNA gyrase.…”

“…Marbofloxacin is considered the third generation fluoroquinolone with broad spectrum activity against some gram-positive, gram-negative organisms and Mycoplasma [2][3][4]. It has bactericidal action by a concentration -dependent mechanism [5].…”