重组人肿瘤坏死单抗白细胞介素2融合蛋白在大鼠体内的药代动力学实验研究  

Pharmacokinetics and biodistribution of ^(125)I labeled rhTNT-IL2 in rats following a single intravenous injection

作　　者：张友九[1] 许玉杰[1] 朱然[1] 胡明江[1] 李建祥[1] 陈跃进[1] 王道锦[1] 周立人[1] 范我[1] 

机构地区：[1]苏州大学放射医学与公共卫生学院,江苏苏州215007

出　　处：《中国药理学通报》2005年第8期1013-1016,共4页Chinese Pharmacological Bulletin

摘　　要：目的研究125I标记的重组人肿瘤坏死单抗白细胞介素2融合蛋白(rhTNTIL2)单次静脉注射后在大鼠体内的药代动力学过程。方法用125I标记rhTNTIL2,γ放射免疫计数器检测三氯醋酸(TCA)沉淀前后血浆、组织、尿和粪的放射性计数,用DSA1.0软件拟合药物动力学模型,并计算相应参数。结果125IrhTNTIL2单次静脉注射后在大鼠体内的动力学过程符合三室模型,T12α为1.77～3.03h,T12β为24.58～28.88h,T1/2γ为82.17～114.09h。125IrhTNTIL2在大鼠肝、脾、肺、肾、卵巢等组织器官中有较高的积聚,而脑中放射性活度较小。125IrhTNTIL2主要经肾由尿排泄,给药后24h,67.1%的药物由尿排出。125IrhTNTIL2从粪中排泄的量甚微。结论125IrhTNTIL2在大鼠体内药代动力学过程的研究为其进一步的开发具有指导价值。Aim To investigate the pharmacokinetics and biodistrbution of ^125I labeled rhTNT-IL2 in rats, a novel fusion protein of recombinant human monoclonal antibody of tumour karyon and Interleukin 2 by genetically engineer. Methods Rats were divided into three groups and administrated with 0. 125,0. 25 and 2.5 mg · kg^-1 respectively, and blood, tissues, urine and ordure were taken at exset times. Radioactivity was measured in all samples before and after trichloroacetic acid （TCA） precipitation. Data of blood were analyzed using DSA1.0 software. Results Blood radioactivity in rats decreased tri-exponentially with half-lives of 1.77 ～3.03 h（T1/2α）,24.58～28.88 h（T1/2β）,82.17 ～ 114.09 h（ T1/2γ ）. Liver, spleen, lung, kidney and ovary were the major organs for deposition of ^125 I-rhTNT-IL2 in rats. Urinary excretion represented the major pathway of elimination, with 67.1% of the administrated dose excreted in urine over 24 h. Conclusion These findings indicate that rhTNT-IL2 has a potential therapeutic use in tumour necrosis therapy.

关 键 词：^125I-rhTNT-IL2 大鼠 药代动力学 

分 类 号：R-332[医药卫生] R392.12