桔梗总皂苷对左氧氟沙星在小鼠体内的药动学及组织分布的影响

目的 采用高效液相色谱（HPLC）法测定小鼠血浆及组织中左氧氟沙星含量，研究桔梗总皂苷对其药动学规律及组织分布的影响。方法 180只昆明小鼠随机分为两组，组Ⅰ为单独ig左氧氟沙星78 mg/kg，组Ⅱ为同时ig桔梗总皂苷65 mg/kg与左氧氟沙星78 mg/kg，采用HPLC法测定给药5、15、30、45 min及1、1.5、2、4、8 h后的血浆及肝、肺、肾组织样品中的左氧氟沙星浓度。结果 血浆中内源性物质对待测物无干扰；血浆及各组织在检测浓度范围内呈良好线性关系（r²>0.999）；方法日内和日间精密度、稳定性及提取回收率均符合生物样品检测标准；组ⅠAUC_0-t为（143.593±16.56），组ⅡAUC_0-t为（120.339±15.542），与组Ⅰ比较，组Ⅱ的AUC明显减小，T_1/2Z显著缩短，T_max明显延长，CLz/F显著增加，C_max及Vz/F无显著性差异；肝、肺、肾组织中左氧氟沙星浓度均迅速提高并快速消除，肺组织中消除速度最快，肺中AUC减少最为明显。结论 合用时，桔梗总皂苷使左氧氟沙星在小鼠体内消除速率明显加快，肺组织中尤为明显，故左氧氟沙星在联合含有桔梗成分的中药治疗肺部疾病时，建议分开服用。

Effects of total saponins of Platycodon grandiflorum on pharmacokinetics and tissue distribution of levofloxacin in mice

Objective To determine the content of levofloxacin in plasma and tissues of mice by high performance liquid chromatography (HPLC), and to study the pharmacokinetics and tissue distribution characteristics after combined with total saponins of Platycodon grandiflorum.Methods 180 Kunming mice were randomly divided into two groups. Group I was ig levofloxacin 78 mg/kg alone, group II was ig platycodon total saponin 65 mg/kg and levofloxacin 78 mg/kg. The concentrations of levofloxacin in plasma and liver, lung and kidney tissues after 5 min, 15 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 4 h, 8 h were determined by HPLC. Results The endogenous substances in plasma have no interference with the test substance. Plasma and tissues have a good linear relationship within the detection concentration range (r² > 0.999). The intra- and inter-day precision, stability and extraction recovery rate are consistent with biological sample detection standard. Group IAUC_0-t was (143.593 ±16.56), group IIAUC_0-t was (120.339 ±15.542), compared with group I, group II''s AUC is significantly reduced, T_1/2Z was significantly shortened, T_max was significantly prolonged, CLz/F was significantly increased, and there was no significant difference between C_max and Vz/F. The concentration of levofloxacin in liver, lung and kidney tissues increased rapidly and fast eliminated. Eliminates the fastest in lung tissue and AUC reduction is most obvious in lung tissue. Conclusion When taken simultaneously, the total saponin of Platycodon grandiflorum significantly accelerated the elimination rate of levofloxacin in mice. Levofloxacin is recommended to be taken separately in combination with traditional Chinese medicine containing Platycodon grandiflorum for the treatment of lung diseases.