ELISA法研究新型重组人肿瘤坏死因子在小鼠体内的药代动力学  

Pharmacokinetic study of novel recombinant human tumor necrosis factor-α (nrhTNF-α) in mice using ELISA

作　　者：鞠洋[1] 路莉[1] 吴勇杰[1] 高明堂[1] 李文广[1] 闵光宁[1] 

机构地区：[1]兰州大学甘肃省中药新药临床前研究重点实验室

出　　处：《中国药理学通报》2005年第7期847-851,共5页Chinese Pharmacological Bulletin

摘　　要：目的研究新型重组人肿瘤坏死因子(nrhTNFα)在小鼠体内的药代动力学。方法给小鼠分别im和ivnrhTNFα后,按不同时间点采血,分离血清,采用双抗体夹心ELISA法测定血清中nrhTNFα的浓度,用DAS药动学软件进行曲线拟合并计算参数。结果nrhTNFα5.51μg·kg-1、24.60μg·kg-1小鼠im后药动学特征符合一室开放模型,呈一级动力学消除。nrhTNFαim给药能迅速吸收入血,Tmax分别为0.17h和0.33h。T1/2分别为1.25h和0.73h,AUC随剂量增加而成比例增加。nrhTNFα5.51μg·kg-1小鼠iv后符合二室开放模型,呈一级动力学消除,T1/2β为0.37h,AUC为771.24ng·L-1·h-1。结论nrhTNFαim和iv的药动学行为在小鼠体内分别符合一室和二室开放模型,均呈一级动力学消除。im给药的生物利用度为48.84%,可考虑作为替代iv的一种安全给药途径。Aim To study the pharmacokinetics of nrhTNF-α in mice. Methods Enzyme-linked immunosorbent assay (ELISA) was used to detect nrhTNF-α in serum. Pharmacokinetic parameters were calculated with DAS software.Results The concentration-time curves of nrhTNF-α fit one-compartment open model after im administration to mice at dose of 5.51 μg·kg -1and 24.60 μg·kg -1. nrhTNF-α entered into circulation rapidly,exhibited first-order kinetic elimination simultaneously.T_ max of nrhTNF-α was 0.17 h and 0.33 h, respectively. T_ 1/2 of nrhTNF-α was 1.25 h and 0.73 h, respectively. The AUC increased in proportion to the dose of nrhTNF-α. The concentration-time curve fit two-compartment open model after iv administration to mice at dose of 5.51 μg·kg -1, exhibited first-order kinetic elimination simultaneously. T_ 1/2β was 0.37 h. AUC was 771.24 ng·L -1·h. Conclusion Pharmacokinetic model of nrhTNF-α after im or iv is consistent with one- or two-compartment open model,and features first-order kinetic elimination simultaneously. The bioavailability of nrhTNF-α after im administration is 48.84%. Intramuscular administration may be an effective and safe alternative to intravenous administration.

关 键 词：肿瘤坏死因子-Α 药代动力学 ELISA 小鼠 

分 类 号：R-332[医药卫生] R392.11