新型重组人肿瘤坏死因子药代动力学的实验方法  

Pharmacokinetic methods for new recombinant human tumor necrosis factor alpha

作　　者：赵宁[1] 张英起[1] 王增禄[1] 刘昌孝[2] 陈拯民[2] 顾以保[2] 蔡永明[2] 高连用[2] 李全胜[2] 曾勇[2] 

机构地区：[1]第四军医大学生物技术中心,陕西西安710033 [2]国家医药管理局天津药物研究院,天津300193

出　　处：《第四军医大学学报》2002年第10期953-955,共3页Journal of the Fourth Military Medical University

基　　金：全军"八五"科技攻关课题 (91C0 41-0 15 6)

摘　　要：目的　为探讨新型重组人肿瘤坏死因子 (nr TNFα)药代动力学而建立生物样品中 nrh TNFα的检测方法 .方法　 1方法 (RA) :动物肌注 1 2 5 标记的 nrh TNFα后 ,测定各生物样品中的总放射活性 ;2方法 (HPL C- RA) :上述生物样品先经 HPL C分离后 ,收集并测定其中 1 2 5 - nrh TNFα部分的放射活性 ;3方法 EIL ISA法 .结果　 RA,HPL C- RA法检测的 nrh TNFα质量浓度与放射性呈直线相关 (RA,r=0 .999HPL C- RA,r=0 .999) .EL ISA法证明 rh TNFα的酶联免疫检测药盒适用于 nrh TNFα的检测 ,rh TNFα的标准曲线与 nrh TNFα的标准曲线显正相关 ,r=0 .994 .这一检测系统与其他细胞因子包括 IFNα,TNFβ,IL- 2和 IL- 6无交叉反应 .结论　 RA,HPL C- RA和 EL ISA法均可作为 nrhAIM To establish three methods of detecting nrh TNFα in biological samples for investigating the pharmacokinetics of nrhTNFα. METHODS Method I(RA): Measuring the total radioactivity in biological samples after 125 Ⅰ nrhTNFα administration by im injection to animals. Method Ⅱ(HPLC RA): Collecting and measuring the radio activity of 125 Ⅰ nrhTNFα after samples separated by HPLC. Method Ⅲ: ELISA. RESULTS The mass concentrations of nrhTNFα measured by RA and HPLC RA had straight line correlation with their radioactivity. It was demonstrated that the rhTNFα ELISA kit was suitable for nrhTNFα detection and both standard curves of rhTNFα and nrhTNFα had a good positive correlation with a correlation coefficient of 0.994. The ELISA system showed no cross reaction with any other cytokines including IFNα, TNFβ, IL 2 and IL 6. CONCLUSION Three methods (RA, HPLC RA, and ELISA) established for detecting nrhTNFα in biological sampis could be used as pharmacokinetic methods of nthTNFα.

关 键 词：肿瘤坏死因子Α 药代动力学 放射测量术 HPLC ELISA 

分 类 号：R969.1[医药卫生—药理学]