中文摘要：

【目的】建立小鼠肺部感染多杀性巴氏杆菌Pasteurella multocida模型,研究马波沙星在健康小鼠和肺部感染的小鼠体内的药动学,通过分析比较两者的药动学参数,优化临床给药。【方法】采用气管插管法对小鼠进行肺部感染,对感染小鼠和健康小鼠按体质量单剂量皮下注射2 mg·kg^-1的马波沙星,用高效液相色谱法测定血浆中马波沙星的浓度。用Win Nonlin5.2.1软件提供的非房室模型处理血浆药物浓度-时间数据。【结果】马波沙星在感染小鼠体内得到的药时曲线下面积（AUC）为4.58μg·m L^-1·h、峰质量浓度（Cmax）为0.97μg·m L^-1、平均滞留时间（MRT）为5.62 h,均显著高于（P〈0.05）在健康小鼠体内得到的AUC（1.67μg·m L^1·h）、Cmax（0.68μg·m L^-1）、MRT（2.63 h）,而表观分布容积（V/F）3.12 L·kg^-1和体清除率（Cl/F）0.42 L·kg^-1·h^-1均显著低于（P〈0.05）健康小鼠体内的V/F（8.61 L·kg^-1）和Cl/F（1.07 L·kg^-1·h^-1）。【结论】多杀性巴氏杆菌感染显著增加了马波沙星的AUC、Cmax、MRT,并降低了V/F、Cl/F,而其他药动学参数无显著性差异。

英文摘要：

[ Objective ] On the basis of the infection, the present study was conducted establishment of a mouse lung model of Pasteurella multocida to characterize the pharmacokinetic properties of marbofloxacin in both healthy and infected mice, and to optimize clinical efficacy by analyzing and comparing the phar- macokinetic 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 ana- lyzed by the noncompartment model of WinNonlinS. 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 C and 2.63 h MRT （ P 〈 0.05 ）. However, the apparent volume of distribu- tion （V/F） was 3.12 L ·kg^-1 and clearance （C1/F） Was 0. 42 L ·kg^-1 ·h^-1 for marbofloxacin in infec- ted 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^-1 C1/F （P 〈 0. 05 ）. [ Conclusion ] P. multocida infection significantly increased the AUC, C MRT of marbofloxacin, reduced the V/F, C1/F,but had no significant impact on the other pharma- cokinetic parameters of marbofloxacin.