Pharmacokinetics and pharmacodynamics of a novel amoxicillin/sulbactam/prednisolone intramammary infusion in lactating cows after repeated administrations
The aim of this study was to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of a novel anti-mastitis preparation, amoxicillin/sulbactam/prednisolone intramammary infusion (CAIMM), containing 200 mg amoxicillin, 50 mg sulbactam and 10 mg prednisolone per 3 g formulation, in healthy lactating cows after repeated administrations. A parallel study was performed using the available combination product (Synulox<sup>®</sup> LC) from Pfizer, with the aim of comparing the two formulations. The concentrations of drugs in quarter milk were determined using the ultra-high performance liquid chromatography tandem mass spectrometric (UPLC-MS/MS) method. No significant difference in the major PK parameters (C<sub>max</sub>, T<sub>max</sub>, MRT, t<sub>1/2λ</sub>, and AUC<sub>last</sub>) was observed. The MIC<sub>90</sub> determined in 106 isolated Staphylococcus spp., 64 Streptococcus spp. and 18 Escherichia coli strains was 0.5, 0.25 and 2 μg/ml, respectively. The PK/PD evaluation showed that the effective duration of action (t > MIC<sub>90</sub>) for CAIMM (42 ± 2.46 h) was increased by 0.86 times compared with Synulox<sup>®</sup> LC (34 ± 3.17 h), but the difference was not significant (P > 0.05). This pharmacokinetic and pharmacodynamic study revealed that CAIMM maintained high concentrations in quarter milk for the three ingredients after repeated intramammary administrations and a similar efficacy was achieved with Synulox<sup>®</sup> LC.