新型重组人肿瘤坏死因子在小鼠体内的药代动力学  

Pharmacokinetics of new recombinant human tumor necrosis factor alpha in mice

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

机构地区：[1]第四军医大学科研部生物技术中心,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12期1065-1067,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　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　采用 1 2 5I标记的 nrh TNFα同位素法 ,观察 im和 iv后的体内过程 .结果　按 10 ,2 0和 4 0μg· kg- 1 3个剂量给小鼠 im nrh TNFα后在 1～ 2 h达到峰浓度 ,总放射性在体内消除较快 ,t1 / 2 为 4 .7～ 6 .5 h,所得结果均证明 Cmax和 AU C与剂量呈显著相关 (r=0 .95 ) ,与 iv给药 (10μg· kg- 1 )的血药浓度进行绝对生物利用度试验 ,其 im给药生物利用度为 0 .80 3.nrh TNFα在体内的分布以肾含量最高 ,脑浓度最低 ,但都低于同时间的血药浓度 .按 10 μg·kg- 1 im给药后 ,用 RA法测定尿和粪 2 4 h放射性总量 ,尿中放射性回收率为 86 .8% ,粪中回收率为 9.5 % ,总排泄量达给药剂量的 96 .3% .结论　 nrhAIM To study the pharmacokinetics of new recombinant human tumor necrosis factor alpha (nrhTNFα) in mice. METHODS 125 I isotope labelled nrhTNFα methods were used. RESULTS nrhTNFα can rapidly enter into blood circulation after the mice are given nrhTNFα im in 10 μg·kg -1 , 20 μg·kg -1 and 40 μg·kg -1 in then it reached the peak concentration in 1~2 h, t 1/2 was 4.7~6.5 h. The results from the three doses demonstrate that C max and AUC are related to doses significantly. The absolute bioavailability of nrhTNFα given imwas 0.803, compared with blood concentrations obtained by iv in 10 μg·kg -1 . The levels of nrhTNFα in blood ranked first, kidney second, and brain last. After the mice are injected im in 10 μg·kg -1 , 86.8% radioactivity is recovered from urine, 9.5% from feces, total discharge amount is up to 96.3% of the amount given. CONCLUSION The pharmacokinetic of nrhTNFα in mice could be applied to two compartment model.

关 键 词：肿瘤坏死因子Α 药代动力学 放射测量术 小鼠 

分 类 号：R969.1[医药卫生—药理学]