【作者】 许杜娟； 黄灿； 苏涌； 杨翠； 陈小欢； 彭万仁； 夏泉；

【Author】 Du-Juan Xu;Can Huang;Yong Su;Cui Yang;Xiao-Huan Chen;Wan-Ren Peng;Quan Xia;Department of Pharmacy,the First Affiliated Hospital of Anhui Medical University;Department of Pharmacy,Affiliated Anqing Hospital of Anhui University;School of Pharmacy,Anhui Medical University;Department of Oncology,the First Affiliated Hospital of Anhui Medical University;

【机构】 安徽医科大学第一附属医院药剂科； 安徽医科大学附属安庆医院药剂科； 安徽医科大学药学院； 安徽医科大学第一附属医院肿瘤科；

【摘要】 目的:观察注射用紫杉醇脂质体（力朴素）与普通紫杉醇注射相比在人体及动物模型中药代动力学差异,以及在血液和组织中的分布特征。方法:采用乙腈蛋白质沉淀法提取血浆中的紫杉醇,反相高效液相色谱法测定人血浆、SD大鼠及荷瘤鼠血浆及组织中紫杉醇的浓度^[1]。结果:两种制剂在SD大鼠中的药动学参数如下:紫杉醇脂质体组,T_1/2:9.239±10.426,t_max:0.167±0.091,C_max:21.837±11.564,CL:0.625±0.197,AUC_（0^∞）:10.562±3.762,Vd:8.347±10.893;普通紫杉醇注射液组,T_1/2:1.952±0.594,t_max:0.111±0.068,C_max:7.098±3.174,CL:0.922±0.419,AUC_（0-∞）:7.701±3.349,Vd:2.378±1.037。紫杉醇注射液和注射紫杉醇脂质体在大鼠和荷瘤鼠肿瘤、肝、脾和肺组织分布较多（有统计学意义P<0.05/0.01）,而在心脏、肾脏分布较少,脂质体组在肝脏和脾脏的药物浓度明显高于普通组（差别有统计学意义）。结论:紫杉醇脂质体具有缓释和长效作用,在在体内具有较长的半衰期和较大的吸收,且发生不良反应的概率较小。更多还原

【Abstract】 Objective:The pharmacokinetics differences in rats and BALB/c Nude mice were investigated between paclitaxel liposome and paclitaxel injection.Simultaneously,the pharmacokinetics of 7 patients with advanced malignant solid tumors administrated paclitaxel liposome were evaluated.Methods:Concentrations of paclitaxel were determined in human plasma,SD rats,BALB/c Nude mice plasma and tissue by reverse phase high performance liquid chromatography（RP-HPLC）.Results:For the pharmacokinetics studies in SD rats,AUC of paclitaxel liposome were apparently larger paclitaxel injection,.Paclitaxel liposome concentrations were significantly higher than paclitaxel injection in liver and spleen.Main pharmacokinetic parameters of paclitaxel liposome in seven cancer patients are as follows:AUCo-t was 9.552±3.079 mg-h-L"1;AUCo- was 27.229±12.634mg·h·L^-1;the half-life(T_1/2) was 4.008+4.864 h;CLz) was 17.905±9.626 L·h^-1·kg^-1;C_maxwas 3.301±1.223 mg·L^-1;and Vz was 106.576±129.853 L·kg^-1.Conclusion:Compared with paclitaxel injection,paclitaxel liposome could produce sustained-release and long-acting effect,attributing to longer half-life and better absorption in the body.更多还原