【摘要】 用1 2 5I标记重组的肿瘤坏死因子 (rTNFα) ,作小鼠体内示踪实验 ,观察其体内分布、代谢和排泄过程。小鼠药代动力学研究结果表明 ,iv后消除相半衰期约 7h ,AUC与剂量呈线性关系。im后生物利用度为2 9% ,峰浓度出现于给药后 2h。分布实验测定iv后各时间每克湿组织中所含rTNFα的浓度 ,在给药后 ,骨髓中浓度与血浆中相等且并行下降 ,脾、肺、肾中的浓度与血液中相近 ,0 5h前以肝内浓度最高 ,但胃中浓度在给药后 2～ 8h达高峰 ,为血浆中浓度的 5倍 ,远高于其它组织 ,小肠中浓度也随后略有升高 ,但低于胃 ,高于其他组织。血浆电泳发现有 2个主要放射峰 ,一为原形药物 ,另一为分子量较大的代谢产物。该代谢物占的比例在15min时为 2 9% ,到 4h升至 63 % ,而原形药物从 15min时的 3 9%降至 2 3 %。血中低分子代谢产物很少 ,但在尿样中 75 %以上为低分子量代谢产物。小鼠静注rTNFα后 ,2 4h尿粪总排出为给药剂量的 87%。更多还原

【Abstract】 The distribution, metabolism and excretion of recombinant tumor neucrosis factor in mice were studied. Recombinant tumor neucrosis factor was labeled with radioactivity iodium 125 , then it was used for tracing in mice. The experimental results indicated that the T1/2 in elimination phase was 7 hours, and AUC was linearly related to the dosage. The bioavailability after im was 29%, the Tmax was at 2 h. The concentration of each gram of wet tissue after iv TNF was measured at various time. At 0 5h the maximum concentration was in the liver , the radioactivity in the marrow equaled in the plasma and decreased parallelly. The concentration in the lung, kidney, and spleen were close in the blood, however, it was 5 folds in the stomach comparing to which in the plasma between 2～8 h, much higher than that in other tissues including liver and kidney. The concentration in small intestine increased subsequently, but lower than stomach and higher than other tissues. There were two radioactivity peaks in the plasma by electrophoresis, one was former, the other was metabolic, product with higher molecular weight. At 15min the percentage of the metabolic product in plasma was 29% of total radioactivity, then increased to 63% at 4 h, but at the same time the former decreased from 39% to 23%. Lower molecular weight product show only in urine during 4 hours, which was 75% of total radioactivity. 87% of dosage was excreted in urine and feces within 24hours. The distribution of TNF in the stomach was higher than that in other tissues , because the stomach may be its primary elimination path. It is worth to study in the treatment of gastric carcinoma.更多还原