【摘要】 目的 研究新型肺靶向多西他赛脂质体（DTX-LP）在原位肺癌模型兔中的药动学行为。方法 采用超高效液相色谱-二级串联质谱（UPLC-MS/MS）法测定DTX在兔血浆中的含量，并进行方法学考察。采用胸腔微创穿刺术制备原位肺癌模型兔，然后随机分为多西他赛注射液（DTX-IN）组和DTX-LP组，耳缘静脉注射给予相应药物，给药剂量均为1.0 mg/kg（以DTX计），然后于5、15、30、60、90、120、240、480 min时取血，测定血浆中DTX浓度。采用DAS 3.3软件进行拟合与分析，并计算药动学参数。结果本研究所用UPLC-MS/MS法的准确度、精密度良好，符合生物样品分析要求。与DTX-IN组比较，DTX-LP组的药-时曲线趋势较平缓，各时间点的血药浓度更低，c_max、t_1/2、AUC_{0→480 min}、AUC_0→∞均显著降低（P<0.05）。结论 DTX-LP在血浆中的暴露量较DTX-IN降低，提示其能快速地从体循环中分布到肺靶器官。更多还原

【Abstract】 OBJECTIVE To study the pharmacokinetic behavior of novel lung-targeted Docetaxel liposome（DTX-LP） in insitu lung cancer model rabbit. METHODS The content of DTX in rabbit plasma was determined by UPLC-MS/MS, and methodology investigation was conducted. in-situ lung cancer model rabbit was made by the ultra-minimal invasive percutaneous puncture inoculation method. Model rabbits were randomly divided into Docetaxel injection（DTX-IN） group and DTX-LP group. The rabbits were given relevant medicine via ear vein at a dose of 1.0 mg/kg（calculated by DTX）; blood was taken at 5, 15, 30, 60, 90, 120, 240 and 480 minutes to measure the concentration of DTX in plasma. DAS 3.3 software was adopted for fitting and analysis, and to calculate pharmacokinetic parameters. RESULTS UPLC-MS/MS method used in this study was accurate and precise, which met the requirements of biological sample analysis. Compared with DTX-IN group, drug concentration-time curve of DTX-LP was smoother, the blood concentration at each time point was lower, and cmax, t_1/2, AUC_0→480 min and AUC_0→∞ were significantly decreased（P<0.05）. CONCLUSIONS The drug exposure of DTX-LP in plasma is significantly reduced than DTXIN, indicating it can be rapidly distributed from systemic circulation to liver target organs.更多还原