重组葡激酶脂质体大鼠体内的药物动力学  

Pharmacokinetics of recombinant staphylokinase (r-Sak) liposomes in rats

作　　者：常艳艳[1] 杨丽[1] 肖萍 史彩虹[1] 游劲松[1] 李皓[1] 

机构地区：[1]沈阳药科大学药学院 [2]北京斯诺尔生物技术有限责任公司

出　　处：《中国药剂学杂志（网络版）》2008年第4期184-190,共7页Chinese Journal of Pharmaceutics：Online Edition

摘　　要：目的比较重组葡激酶(r-Sak)溶液及其脂质体制剂大鼠静脉注射给药后体内药物动力学过程,为重组葡激酶脂质体的研究奠定基础。方法正常大鼠以0.9mg·kg-1剂量分别静脉注射重组葡激酶溶液及重组葡激酶脂质体,不同时间取血,应用溶圈法测定血浆中药物浓度,比较两种制剂在正常大鼠体内的药物动力学过程。利用三氯化铁法建立大鼠颈动脉血栓模型,以0.9mg·kg-1剂量尾静脉注射重组葡激酶脂质体,应用溶圈法测定不同时间血浆药物浓度,比较重组葡激酶脂质体在正常大鼠和血栓大鼠体内的药物动力学过程。用3p97药物动力学程序处理数据,求算各药物动力学参数。结果重组葡激酶溶液及其脂质体制剂静脉注射给药,在正常大鼠及血栓大鼠体内的平均血药浓度-时间数据经3p97拟和均符合二室模型。静脉注射重组葡激酶脂质体在正常大鼠体内消除半衰期和AUC分别为129.79min和4692.52mg·min·L-1,分别是其溶液剂的12.5和10.4倍,均具有显著性差异(p【0.001,p【0.001),而重组葡激酶脂质体在正常大鼠与血栓大鼠体内的消除半衰期和AUC无显著性差异(p】0.05,p】0.05)。结论脂质体作为重组葡激酶的载体,可以显著延长重组葡激酶的体内消除半衰期,增大AUC,对提高药物疗效具有实用意义。Objective To investigate the pharmacokinetics of recombinant staphylokinase (r-Sak) solution and r-Sak liposomes in normal rats and thrombosis rats.Methods r-Sak solution and r-Sak liposome formulation were administrated intravenously to normal rats at a dose of 0.9 mg·kg-1 individually.Cervical arterial thrombosis model was developed in rats by a ferric chloride method.r-Sak liposomes were also administrated intravenously to the thrombosis rats at the dose of 0.9 mg·kg-1.The fibrinolytic activities of r-Sak were determined by a "lytic circle" method.The pharmacokinetic parameters of r-Sak solution and r-Sak liposomes were caculated by 3p97 program.Results The plasma concentration time curve fitted with 2-compartment model after intravenous administration of r-Sak solution and r-Sak liposomes in rats.For r-Sak liposomes group,the terminal half life(t1/2β) and the area under the plasma concentration time curve(AUC) were 129.79 min and 4692.52 mg·min·L-1,respectively,which were 12.5 and 10.4 times higher than that of the r-Sak solution group.However,no significant difference in t1/2β and AUC values were found after intravenous administration of r-Sak liposomes to normal rats and thrombosis rats(P>0.05).Conclusion Liposomes as the carrier of r-Sak can remarkably prolong its terminal half life and AUC,implying its potential in clinical application.

关 键 词：药剂学 脂质体 溶圈法 重组葡激酶 血栓模型 药物动力学 

分 类 号：R96[医药卫生—药理学]