小鼠注射新型重组人肿瘤坏死因子的药代动力学

Pharmacokinetic study of new recombinant human tumor necrosis factor (nrhTNF α) in mice

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

AIM To study the pharmacokinetics of nrhTNF α in mice. METHODS Both methods of HPLC RA (Measuring the radioactivity of 125 I nrhTNF α after sample separated with HPLC) and Enzyme linked immunosorbent assay (ELISA) were used to detect nrhTNF α in serum. RESULTS nrhTNF α entered into circulation rapidly after im injection to mice at doses of 10, 20 and 40 μg·kg -1 . The time to reach maximum serum concentration of nrhTNF α was 0.5 h. The levels of undegraded nrhTNF α in kidney ranked first, blood second, lung third, liver fouth, and brain last. The half life ( T 1/2 ) of nrhTNF α was in 0.6~1 h. The Cmax and AUC were correlated with dosage for both methods. Comparing with iv injection, the absolute bioavailability after im injection was 0.166, indicating that nrhTNF α was easy to be metabolized and eliminated in the body. CONCLUSION The above results demonstrate the pharmacokinetics of undegraded nrhTNF α in mice.