~(125)I-MIL50在大鼠体内的药代动力学及生物分布

为探究~(125)I标记重组抗蓖麻毒素(Ricin)人源化单克隆抗体(~(125)I-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~(125)I标记,结合TCA法测定不同时间~(125)IMIL50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14d内没有差异,14d后染毒组~(125)I-MIL50消除快于未染毒组;血清中~(125)I-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;~(125)I-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。

Pharmacokinetics and Biodistribution of 125 I-MIL50 in Wistar Rats

In order to study the impact of Ricin on the pharmacokinetics of 125 I-M IL50 and to investigate the tissue distribution and excretion of 125 I-M IL50 in Wistar rats , MIL50 was labeled with 125 I using the Iodogen method .Then ,the concentration of 125 I-MIL50 in serum、tissues、body fluids and excretions was measured by TCA method at different time .The results showed that 25I-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 125 I-MIL50 when the concentration of 125 I-MIL50 was low in Wistar rats .It might because of the interaction between antigen and antibody .125 I-MIL50 had no specific combination with tissues and it could hardly entered into lipophilic tissues .Urinary excretion repre-sented the major pathway of elimination of 125 I-MIL50 .The results of the study provide a reference for clinical trials and drug administration program .