Abstract:
Objective On the basis of the establishment of a mouse lung model of Pasteurella multocida infection, the present study was conducted to characterize the pharmacokinetic properties of marbofloxacin in both healthy and infected mice, and to optimize clinical efficacy by analyzing and comparing the pharmacokinetic parameters.
Method Neutropenic mice were infected with P. multocida using endotracheal intubation. The lung infected and healthy mice were each administrated a single subcutaneous dose of 2 mg·kg-1 marbofloxacin based on their body masses. Marbofloxacin concentrations in the plasma were measured by high performance liquid chromatography. The plasma drug concentration-time data were analyzed by the noncompartment model of WinNonlin5.2.1 software.
Result For marbofloxacin in infected mice, the area under the plasma drug concentration-time curve (AUC) was 4.58 μg·mL-1·h, the maximum concentration (Cmax) was 0.97 μg·mL-1 and mean residence time (MRT) was 5.62 h, which were all significantly higher compared to marbofloxacin in healthy mice with 1.67 μg·mL-1·h AUC, 0.68 μg·mL-1 Cmax, and 2.63 h MRT (P < 0.05). However, the apparent volume of distribution (V/F) was 3.12 L·kg-1 and clearance (Cl/F) was 0.42 L·kg-1·h-1 for marbofloxacin in infected mice, both were significantly lower than those in healthy mice with 8.61 L·kg-1 V/F and 1.07 L·kg-1·h-1Cl/F (P < 0.05).
Conclusion P.multocida infection significantly increased the AUC, Cmax, MRT of marbofloxacin, reduced the V/F, Cl/F, but had no significant impact on the other pharmacokinetic parameters of marbofloxacin.
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