马波沙星在健康小鼠和感染多杀性巴氏杆菌小鼠体内的药动学比较
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Comparison of pharmacokinetics of marbofloxacin in healthy mice and in mice infected with Pasteurella multocida
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    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WinNonlin5.2.1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4.58 μg·mL-1·h、峰质量浓度(Cmax)为0.97 μg·mL-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 (1.67 μg·mL-1·h)、Cmax (0.68 μg·mL-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。

    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-1Cl/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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瞿颖,卢燕,孙美珍,李晓虹,仇珍珍,曹长福,曾振灵.马波沙星在健康小鼠和感染多杀性巴氏杆菌小鼠体内的药动学比较[J].华南农业大学学报,2016,37(2):14-19

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  • 收稿日期:2015-05-07
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  • 在线发布日期: 2016-02-02