【摘要】 目的:建立人血浆中紫杉醇(paclitaxel,PTX)浓度的液相色谱-质谱(liquid chromatography-mass spectometry,LC-MS)检测方法,比较注射用紫杉醇脂质体(paclitaxelliposomeforinjection,L-PTX)和常规紫杉醇注射液(conventional paclitaxel injection,C-PTX)在肿瘤患者中的药动学特征。方法:采用随机、开放和对照的试验设计方案。试验分2组,每组各8例患者,分别静脉滴注175mg/m2L-PTX或C-PTX,并于静脉滴注过程中的1.5和3h及滴注结束后的0.25、0.5、1、2、4、8、12、24、36、48和72h采集受试者血样。LC-MS法测定血药浓度,应用DAS2.0软件计算药动学参数并进行比较。结果:患者单次静脉滴注175mg/m2L-PTX与C-PTX的主要药动学参数:血浆峰浓度(Cmax)分别为6455±2247和7400±1542μg/L;药物血浆浓度-时间曲线下面积(area under the plasma concentration-time curve,AUC0-∞)分别为14812±2846和21693±2657μg·h·L-1;血浆消除半衰期(t1/2z)分别为30.5±7.3和13.7±3.2h;表观分布容积(Vz)分别为526.8±112.1和162.9±49.1L/m2;血浆清除率(plasmaclearance,CLz)分别为12.3±2.7和8.2±1.0L·h-1·m-2。经统计学分析,2组的药动学参数差异有统计学意义(P<0.05)。结论:脂质体包裹后改变了PTX的体内药动学特性,与常规PTX相比,脂质体制剂在肿瘤患者体内的分布特性和消除情况有显著不同,具有更好的组织亲和性与缓释作用。更多还原

【Abstract】 Objective:To establish a liquid chromatography-mass spectometry(LC-MS) method for determination of paclitaxel in human plasma,and to study the pharmacokinetics of paclitaxel liposome for injection(L-PTX) and conventional paclitaxel injection(C-PTX) in patients with cancer.Methods:An open,randomized and controlled study was designed.Sixteen patients with cancer were divided into two groups receiving a single dose of 175 mg/m2 L-PTX and C-PTX,respectively.The blood samples were collected at 1.5 and 3 h during intravenous infusion and at 0.25,0.5,1,2,4,8,12,24,36,48 and 72 h after the end of infusion.The drug concentration in the blood was determined by LC-MS method,and the pharmacokinetic parameters were calculated by DAS2.0 software and compared.Results:The main pharmacokinetic parameters of L-PTX and C-PTX after a single intravenous infusion of 175 mg/m2 were as follows:peak plasma concentrations(Cmax) were 6 455 ± 2 247 μg/L and 7 400 ± 1 542 μg/L;the areas under the plasma concentration-time curve(AUC0-∞) were 14 812 ± 2 846 μg·h·L-1 and 21 693 ± 2 657 μg·h·L-1;the plasma elimination half-life(t1/2z) were 30.5 ± 7.3 h and 13.7 ± 3.2 h;the apparent volumes of distribution(Vz) were 526.8 ± 112.1 L/m2 and 162.9 ± 49.1 L/m2;the plasma clearance rates(CLz) were 12.3 ± 2.7 L·h-1·m-2 and 8.2 ± 1.0 L·h-1·m-2,respectively.The statistical analysis showed that there was a significant difference in major pharmacokinetic parameters between L-PTX andC-PTX(P<0.05).Conclusion:The pharmacokinetic properties of paclitaxel in vivo are changed when it is encapsulated by liposome.Compared with C-PTX,the L-PTX is uniquely different in distribution and elimination aspects in patients with cancer,and it demonstrates improved tissue affinity and effect of delayed release.更多还原