Pharmacokinetic-pharmacodynamic relationship of marbofloxacin for Escherichia coli and Pasturella multocida following repeated intramuscular administration in goats.

Abstract

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin (MBF) were determined in six healthy female goats of age 1.00-1.25years after repeated administration of MBF. The MBF was administered intramuscularly (IM) at 2mgkg-1 day-1 for 5days. Plasma concentrations of MBF were determined by high-performance liquid chromatography, and PK parameters were obtained using noncompartmental analysis. The MBF concentrations peaked at 1hr, and peak concentration (Cmax ) was 1.760µg/ml on day 1 and 1.817µg/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±0.719µg×hr/ml) and day 5 (AUC0-∞ D5=8.70±0.857µg×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 5days. Minimum inhibitory concentration (MIC) demonstrated that Escherichia coli (MIC=0.04µg/ml) and Pasturella multocida (MIC=0.05µg/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 2mgkg-1 day-1 is appropriate to treat infections caused by E. coli. However, a dose of 5mgkg-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 2mg/kg in goats without risk of drug accumulation up to 5days.