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Pharmacokinetics and Biodistribution of 125I-MIL50 in Wistar Rats

LEI Xiao1,2;ZHU Xiao-xia2;WANG De-cai1;MENG Zhi-yun2;GAN Hui2;GU Ruo-lan2;WU Zhuo-na2;ZHENG Ying2;LI Jian2;Lv Ming3;DOU Gui-fang2   

  1. 1.Taishan Medical University, Tai’an 271000, China;2.Institute of Transfusion Medicine, Academy of Military Medical Science, Beijing 100850, China;3.Institute of Basic Medical Science, Academy of Military Medical Science, Beijing 100850, China
  • Online:2016-05-20 Published:2016-06-03

125I-MIL50在大鼠体内的药代动力学及生物分布

雷晓1,2;朱晓霞2;王德才1;孟志云2;甘慧2;顾若兰2;吴卓娜2;郑颖2;李俭2;吕明3;窦桂芳2   

  1. 1.泰山医学院,山东 泰安271000;2.军事医学科学院 野战输血研究所,北京100850;3.军事医学科学院 基础医学研究所,北京100850

Abstract:

In order to study the impact of Ricin on the pharmacokinetics of 125I-MIL50 and to investigate the tissue distribution and excretion of 125I-MIL50 in Wistar rats, MIL50 was labeled with 125I using the Iodogen method. Then, the concentration of 125I-MIL50 in serum、tissues、body fluids and excretions was measured by TCA method at different time. The results showed that 125I-MIL50 was eliminated faster after 14 days in the Ricin administrated group. The concentration of 125I-MIL50 in serum was always higher than that in other tissues. The level in kidney and bladder were high and in brain, spine and fat were low. The cumulative excretion rate of 125I-MIL50 was 62.6% in urine, and 15.5% in feces within 27 days. Ricin could fasten the elimination of  125I-MIL50 when the concentration of 125I-MIL50 was low in Wistar rats. It might because of the interaction between antigen and antibody. 125I-MIL50 had no specific combination with tissues and it could hardly entered into lipophilic tissues. Urinary excretion represented the major pathway of elimination of  125I-MIL50. The results of the study provide a reference for clinical trials and drug administration program.

Key words: Ricin, 125I-MIL50, pharmacokinetics, biodistribution, excretion

摘要:

为探究125I标记重组抗蓖麻毒素(Ricin)人源化单克隆抗体(125I-MIL50)在大鼠体内的药代动力学、生物分布及排泄特点,采用Iodogen法对MIL50进行125I标记,结合TCA法测定不同时间125I-MIL50在大鼠血清、组织、体液和排泄物中的含量。结果表明:Ricin染毒组和直接给药组血药浓度在14 d内没有差异,14 d后染毒组125I-MIL50消除快于未染毒组;血清中125I-MIL50浓度高于其他组织和体液,肾、膀胱组织中浓度较高,脑、脊髓、脂肪等脂性组织中浓度一直较低;125I-MIL50给药后27d内经尿累积排泄率约为62.6%,经粪便的排泄率为15.5%。研究结果为临床实验和给药方案提供参考依据。

关键词: 蓖麻毒素, 125I-MIL50, 药代动力学, 生物分布, 排泄