The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin (MBF) were determined in six healthy female goats of age 1.00-1.25 years after repeated administration of MBF. The MBF was administered intramuscularly (IM) at 2 mg kg-1 day-1 for 5 days. Plasma concentrations of MBF were determined by high-performance liquid chromatography, and PK parameters were obtained using noncompartmental analysis. The MBF concentrations peaked at 1 hr, and peak concentration (Cmax ) was 1.760 µg/ml on day 1 and 1.817 µg/ml on day 5. Repeated dosing of MBF caused no significant change in PK parameters except area under curve (AUC) between day 1 (AUC0-∞ D1 = 7.67 ± 0.719 µg × hr/ml) and day 5 (AUC0-∞ D5 = 8.70 ± 0.857 µg × hr/ml). A slight difference in mean residence time between 1st and 5th day of administration and accumulation index (AI = 1.13 ± 0.017) suggested lack of drug accumulation following repeated IM administration up to 5 days. Minimum inhibitory concentration (MIC) demonstrated that Escherichia coli (MIC = 0.04 µg/ml) and Pasturella multocida (MIC = 0.05 µg/ml) were highly sensitive to MBF. Time-kill kinetics demonstrated rapid and concentration-dependent activity of MBF against these pathogens. PK/PD integration of data for E. coli and P. multocida, using efficacy indices: Cmax /MIC and AUC0-24hr /MIC, suggested that IM administration of MBF at a dose of 2 mg kg-1 day-1 is appropriate to treat infections caused by E. coli. However, a dose of 5 mg kg-1 day-1 is recommended to treat pneumonia caused by P. multocida in goats. The study indicated that MBF can be used repeatedly at dosage of 2 mg/kg in goats without risk of drug accumulation up to 5 days.
Keywords: E. coli; P. multocida; PK-PD integration; goat; marbofloxacin; time-kill kinetics.
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