左氧氟沙星在肺炎克雷伯菌肺部感染小鼠体内的药动学

目的：建立肺炎克雷伯菌（Klebsiella pneumoniae，Kp）肺部感染小鼠模型，采用高效液相色谱（HPLC）法测定不同剂量左氧氟沙星（levofloxacin，LVF）在其体内的药动学参数。方法：血浆样品经乙腈沉淀蛋白后，采用Diamosail-C₁₈色谱柱分离，流动相为乙腈（0.05 mol·L^-1）-磷酸二氢钾（17∶83），磷酸二氢钾盐溶液以磷酸调整pH为3.0左右，流速为1 mL·min^-1；检测波长为295 nm。结果：LVF在0.3~12 mg·L^-1内线性关系良好；方法的日间和日内精密度均小于7.2%，稳定性良好。Kp肺部感染小鼠口服LVF15，30，60和90 mg·kg^-1后，LVF的PK参数t_max、t_1/2、CL/F和V_d/F均无显著性差异（P>0.05）。结论：所建立的HPLC分析方法准确、灵敏、专属性强、重复性高，适用于肺炎克雷伯菌肺部感染小鼠体内的左氧氟沙星药动学研究。

Pharmacokinetics of levofloxacin in mice with pulmonary infection induced by Klebsiella pneumoniae

OBJECTIVE To develop a HPLC method for determination of levofloxacin (LVF) in mice plasma samples, and to investigate the pharmacokinetic parameters of different doses of LVF in the pulmonary infection mice induced by Klebsiella pneumoniae (Kp).METHODS The plasma samples were precipitated by acetonitrile, and then separated on a Diamosail-C₁₈ column with a mobile phase composed of acetonitrile and potassium dihydrogen phosphate buffer solution (pH=3.0) (17:83, V/V) at a flow rate of 1 mL·min^-1. The detection wavelength was 295 nm.RESULTS The method exhibited good linearity in the concentration range of 0.3-12 mg·L^-1. The values on both the occasions (intra-and inter-day) were all within 7.2%, and LVF was stable in mice plasma under different storage conditions. The pharmacokinetic parameters of t_max, t_1/2, CL/F, V_d/F and K_e showed no significant difference among different dosage groups (P>0.05).CONCLUSION The developed HPLC method is accurate, sensitive, and reproducible, and suitable for the pharmacokinetic study of LVF in mice with pulmonary Kp infection.