用微透析法研究肺炎大鼠灌胃左氧氟沙星的肺部药动学

目的：观察肺炎大鼠模型灌胃左氧氟沙星后在肺组织中的药动学特点.方法：以肺炎链球菌诱导肺炎大鼠模型,之后灌胃左氧氟沙星42 mg/kg.采用微透析技术对大鼠血液和肺组织同步取样,以HPLC法测定血液和肺组织中的药物浓度,计算左氧氟沙星的主要药动学参数和肺组织穿透率.结果：血液和肺组织中的药物浓度变化趋势一致.从第20 min开始,肺组织中的药物浓度始终高于血药浓度.左氧氟沙星的肺组织穿透率为（1.17±0.06）.在血液和肺组织的主要药动学参数分别为：tmax（46.67±20.82）和（43.33±23.09） min,cmax（1.29±0.41）和（1.56±0.70） μg/ml,t12（534.38±381.64）和（591.38±416.08） min,AUCinf（920.33±473.56）和（1196.23±992.35） μg·min·ml-1,在肺组织的分布系数为（1.22±0.56）.结论：肺炎大鼠模型灌胃左氧氟沙星后具有良好的肺组织穿透率和分布系数.

Study on lung pharmacokinetics of gavage levofloxacin in pneumonia rats by microdialysis method

Objective：To study the pharmacokinetic characteristics of lung tissue in pneumonia rats by gavage levofloxacin.Methods.Pneumonia rat model was induced by Streptococcus pneumoniae.The rats were then gavaged levofloxacin at a dose of 42 mg/kg.Blood and lung tissue were sampled in vivo by microdialysis method simultaneously.The concentrations of levofloxacin in blood and lung were measured by HPLC method.Then,main pharmacokinetic parameters and pulmonary penetration rate were calculated.Results：Changes in the concentrations of levofloxacin in the blood and lung tissue were identical.At min 20,the concentration of levofloxacin in the lung tissue was higher than that in the blood.The pulmonary penetration rate of levofloxacin was （1.17±0.06）.The main pharmacokinetic parameters of levofloxacin in the blood and lung tissue were as follows：tmax（46.67±20.82） and （43.33±23.09） min,cmax（1.29±0.41） and （1.56±0.70） μg/ml,t12 （534.38±381.64） and （591.38±416.08） min,AUC0-inf （920.33 ± 473.56） and （1196.23 ± 992.35） μg · min · ml-1,respectively.The distribution coefficient in the lung tissue was （1.22±0.56）.Conclusion：Gavage levofloxacin exhibits good pulmonary penetration rate and distribution coefficient in pneumonia rats.