注射用紫杉醇脂肪乳和普通紫杉醇注射液在比格犬体内的药动学比较  

Comparison of pharmacokinetics between paclitaxel emulsion for injection and paclitaxel injection in beagles

作　　者：李金银[1,2] 李文学[2] 唐原君[2] 陈建明[2] 狄斌[1] 范国荣[2] 

机构地区：[1]中国药科大学药学院药物分析学教研室,南京210009 [2]第二军医大学药学院药物分析学教研室,上海市药物(中药)代谢产物研究重点实验室,上海200433

出　　处：《药学服务与研究》2013年第3期200-204,共5页Pharmaceutical Care and Research

基　　金：国家科技重大专项重大新药创制资助项目(2009ZX09301-011)

摘　　要：目的:建立测定比格犬血浆中紫杉醇浓度的方法,并将其应用于比格犬体内注射用紫杉醇脂肪乳和普通紫杉醇注射液的药动学比较研究。方法:将注射用紫杉醇脂肪乳和普通紫杉醇注射液静脉给药1.5mg/kg后,测定比格犬血浆中的药物浓度,估算并比较药动学数据。血浆样品及内标多西他赛置于96孔板中,进行高通量的液液萃取。结果:紫杉醇的线性范围为2～500ng/ml,最低定量下限为2ng/ml,批内、批间精密度(RSD%)均<15%。分别静脉注射两种制剂后,在比格犬血浆中,紫杉醇的t1/2分别为(4.72±0.53)和(4.50±0.81)h,MRT为(2.46±0.38)和(1.82±0.59)h,AUC0～12h为(388.90±63.39)和(711.74±33.70)ng.h.ml-1,AUC0～∞为(411.89±68.44)和(738.35±45.54)ng.h.ml-1,CL为(3.71±0.46)和(2.04±0.11)L.h-1.kg-1,Vd为(9.07±1.35)和(3.65±0.91)L/kg。结论:该方法灵敏、准确、专一、简便并且实现高通量分析,适用于注射用紫杉醇脂肪乳和普通紫杉醇注射液在比格犬体内的药动学比较研究。两种制剂的主要药动学参数中c0、AUC、CL、Vd存在显著性差异(P<0.05),用梯形面积法(AUC)估算紫杉醇脂肪乳对于紫杉醇普通制剂的相对生物利用度为(54.93±10.82)%。Objective：To establish an analytical method for the determination of paclitaxel,and to investigate and compare the pharmacokinetics of paclitaxel emulsion for injection and paclitaxel injection in beagles.Methods：After intravenous administration of paclitaxel emulsion for injection and paclitaxel injection（1.5mg/kg）,paclitaxel concentrations in plasma of beagles were determined,and pharmacokinetic parameters were calculated.Paclitaxel and docetaxel（internal standard）were isolated from plasma or tissue samples in 96-well plates by liquid-liquid extraction,and most liquid transfer steps were performed by 96/ 384-channel semi-automatic pipetting tools.Results：The calibration curves were linear over the range of 2-500ng/ml.The lowest limit of quantitation was 2ng/ml.The intra-run and inter-run relative standard deviation（RSD）was less than 15%.The main pharmacokinetic parameters of paclitaxel emulsion for injection and paclitaxel injection were as follows：t1/2were（4.72± 0.53）and（4.50±0.81）h,MRT were（2.46±0.38）and（1.82±0.59）h,AUC0-12hwere（388.90±63.39）and（711.74± 33.70）ng.h.ml-1,AUC0-∞were（411.89±68.44）and（738.35±45.54）ng.h.ml-1,CL were（3.71±0.46）and（2.04±0.11）L.h-1.kg-1,Vdwere（9.07±1.35）and（3.65±0.91）L/kg.Conclusion：The method was sensitive,accurate,specific,simple and convenient for the pharmacokinetic study of paclitaxel emulsion for injection and paclitaxel injection in beagles.There were significant differences in the pharmacokinetic parameters of c0,AUC,CL,Vdof the two preparations（P 0.05）.Relative bioavailability of paclitaxel emulsion for injection was（54.93±10.82）%,as calculated by AUC determination.

关 键 词：注射用紫杉醇脂肪乳 紫杉醇注射液 药代动力学 色谱法 高效液相 质谱法 联用 比格犬 

分 类 号：R969.1[医药卫生—药理学] R979.1[医药卫生—药学]