关键词: 肿瘤坏死因子α;药代动力学;放射测量术;小鼠

    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 采用125 I标记的nrhTNFα同位素法，观察im和iv后的体内过程. 结果 按10，20和40μg·kg-1 3个剂量给小鼠im nrhTNFα后在1～2h达到峰浓度，总放射性在体内消除较快，t1/2 为4.7～6.5h，所得结果均证明Cmax 和AUC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0.803.nrhTNFα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10μg·kg-1 im给药后，用RA法测定尿和粪24h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 nrhTNFα在小鼠的体内代动力学符合二室模型.

    Pharmacokinetics of new recombinant human tumor necrosis factor alpha in mice

    ZHAO Ning ZHANG Ying-Qi WANG Zeng-Lu GAO Lian-Yong GU Yi-Bao LI Quan-Sheng CAI Yong-Ming ZENG Yong CHEN Zheng-Min

    LIU Chang-Xiao

    1 Biotechnology Center，Administration of Science Research，Fourth Military Medical University，Xi'an710033，China，

    2 Tianjin Institute of Pharma-ceutical Research，Tianjin300193，China

    Keywords:tumor necrosis factor;pharmacokinetics;radiom-etry;mice

    Abstract:AIM To study the pharmacokinetics of new re-combinant human tumor necrosis factor alpha(nrhTNFα)in mice.METHODS 125 I isotope labelled nrhTNFαmethods were used.RESULTS nrhTNFαcan rapidly enter into blood circulation after the mice are given nrhTNFαim in10μg·kg-1 ......