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目的 研究新型重组人肿瘤坏死因子 (nrh TNFα)在小鼠体内的药代动力学 .方法 给小鼠按 10 ,2 0和 40μg·kg- 1 剂量 im nrh TNFα后 ,不同时间点采血 ,分离血清 ,采用高效液相色谱法 (HPL C)分离结合同位素法和酶联免疫法(EL ISA)测定血清中 nrh TNFα的浓度 .结果 小鼠 im后 ,nrh TNFα能迅速进入血液循环 ,约在 0 .5 h内达到最大血浓度 ,未降解的 nrh TNFα在体内的分布以肾脏最高 ,血液次之 ,其后为肺、肝 ,脑浓度最低 .消除半衰期 (T1 /2 )在 0 .6～ 1h.两种方法所得 Cmax和 AUC与剂量呈显著相关 .与 iv比较 ,im给药 nrh TNFα的绝对生物利用度仅为 0 .16 6 ,表明nrh TNFα在体内易代谢消除 .结论 阐明了 nrh TNFα原型药物在小鼠体内的药代动力学过程
Objective To study the pharmacokinetics of a novel recombinant human tumor necrosis factor (TNFα) in mice.Methods Mice were injected with im nrh TNFα at doses of 10, 20 and 40 μg · kg-1 at different time points, , And the concentration of nrh TNFα in serum was determined by high performance liquid chromatography (HPL C) separation and combination of isotope method and enzyme-linked immunosorbent assay (ELISA) .Results After im, nrh TNFα could quickly enter the blood circulation, Within 5 h, the maximum blood concentration was reached, and the non-degraded nrh TNFα was highest in the kidney and followed by the blood in the body, followed by the lowest concentration in the lung, liver and brain. The elimination half-life (T1 / 2) was between 0.6 h and 1 h. The Cmax and AUC obtained by the two methods were significantly correlated with the dose.Compared with iv, the absolute bioavailability of imh administration of TNFα was only 0.166, indicating that nrh TNFα was abolished in vivo.Conclusion It is demonstrated that nrh TNFα Pharmacokinetics in mice