酶联免疫吸附试验法研究PEG-rhG-CSF与rHSA-hG-CSF在小鼠体内的药代动力学  

Pharmacokinetics of PEG-rhG-CSF and rHSA-hG-CSF in mice determined with ELISA

作　　者：马国昌[1] 陈枢青[1] 朱振洪[2] 黄岩山[3] 潘会强[2] 周金宝[2] 

机构地区：[1]浙江大学药学院,浙江杭州310031 [2]杭州九源基因工程有限公司,浙江杭州310018 [3]浙江大学医学院,浙江杭州310031

出　　处：《药学学报》2007年第2期197-200,共4页Acta Pharmaceutica Sinica

摘　　要：研究重组人粒细胞集落刺激因子(rhG-CSF)、聚乙二醇修饰的重组人粒细胞集落刺激因子(PEG-rhG-CSF)与重组人血清白蛋白-粒细胞集落刺激因子融合蛋白(rHSA-hG-CSF)在小鼠体内的药代动力学,验证两种方法对rhG-CSF半衰期(T1/2)的影响。小鼠分别皮下给药rhG-CSF,PEG-rhG-CSF与rHSA-hG-CSF后,在不同时间点采血并分离血清,采用双抗体夹心酶联免疫吸附试验法测定血清中rhG-CSF的浓度,用3P87药动学软件进行曲线拟合并计算参数。结果显示,rhG-CSF,PEG-rhG-CSF与rHSA-hG-CSF的半衰期(T1/2)分别为2.1,14.2和10.6h,后两者半衰期分别为rhG-CSF的7倍、5倍;PEG-rhG-CSF和rHSA-hG-CSF的达峰时间Tpeak分别为rhG-CSF的15倍、13倍。通过ELISA法检测比较rhG-CSF,PEG-rhG-CSF与rHSA-hG-CSF在小鼠体内的药代动力学,表明PEG修饰与白蛋白融合技术可以延长rhG-CSF的半衰期。Double antibody sandwich-type ELISA was used to detect rhG-CSF in serum to study the pharmacokinetics of rhG-CSF, PEG-rhG-CSF and rHSA-hG-CSF in mice and to confirm that PEGlyation and albumin fusion of rhG-CSF technology can prolong half-life of G-CSF. Pharmacokinetic parameters were calculated with 3P87 software. T1/2s of rhG-CSF, PEG-rhG-CSF and rHSA-hG-CSF are 2. 1 , 14.2 and 10. 6 h, respectively. T1/2s of PEG- rhG-CSF and rHSA-hG-CSF are 7, 5 times than T1/2s of rhG- CSF, respectively. Tpeak S of PEG-rhG-CSF and rHSA-hG-CSF are 15, 13 times than Tpeak of rhG-CSF, respectively. The result of ELISA indicates that PEGlyation and albumin fusion of rhG-CSF technology can prolong half-life of G-CSF.

关 键 词：人粒细胞集落刺激因子 聚乙二醇 白蛋白 药代动力学 ELISA 

分 类 号：R917[医药卫生—药物分析学]