摘要
目的研究125I标记的抗炎抗凝双效融合蛋白TAP-SSL5单次静脉注射后在健康日本大耳兔体内的药代动力学过程。方法采用固相氧化法(Iodogen法)将Na125I直接标记于TAP-SSL5,由耳缘静脉给每只大耳兔注射18.5×103kBq的125I-TAP-SSL5,分别于注射后1.5、3、5、10、30、60、120、240、480 min采血,称量并测定放射性计数(Counts per minute,cpm),换算为血液放射性浓度,经DAS软件分析得出最佳房室模型及相关药代动力学参数。结果纸层析法测得125I-TAP-SSL5的标记率为(67.32±9.91)%,放射化学纯度为(91.62±3.22)%,比活度为(30.2±4.4)TBq/μmol;TAP-SSL5在大耳兔体内的药代动力学过程符合权重为1的二室模型,分布相半衰期(t1/2α)及消除相半衰期(t1/2β)分别为(0.08±0.04)h和(4.97±0.75)h,清除率(Clearance,CL)为(0.015±0.011)ml/h,一室向二室转运常数(K12)为(6.651±3.642)/h,二室向一室转运常数(K21)为(4.072±1.737)/h。结论125I-TAP-SSL5在健康大耳兔体内的药代动力学过程符合权重系数为1的二室模型,自体清除率缓慢,可保证与组织有更多的结合几率。
Objective To investigate the pharmacokinetics of ^125Ⅰ_ tick anticoagulant peptide （TAP）- staphylococcal superantigen like protein-5 （SSL5） in normal rabbits. Methods TAP-SSL5 was labeled directly with Na ^125Ⅰ using the idogen method. The best compartment model and its pharmacokinetic parameters were determined in rabbits （n = 6） by measuring the blood radioactive concentrations at 1.5, 3, 5, 10, 30, 60, 120, 240 and 480 min after bolus injection of 18.5 MBq ^125Ⅰ-TAP-SSL5. Results The labeling rate and radiochemical purity of ^125Ⅰ-TAP-SSL5 was （67.32± 9.91 ） % and （91.62 ± 3.22 ） % respectively. The specific activity was （30.2 ±4.4） TBq/μmol. TAP-SSL5 showed two compartment model in rabbit, the main parameters of pharmacokinetics were as follows ： t_1/2α = （0.08 ± 0.04） h, t_1/2β = （4.97 ± 0.75 ） h, clearance （CL） = 0.015 ±0.011 ml/h, K12 = （6.651 ±3.642）/h, and K21 = （4.072 ± 1.737）/h. Conclusion The pharma- cokinetic of ^125Ⅰ-TAP-SSL5 fits the two compartment model （weight coefficient = 1 ） in normal rabbits. Its clear- ance is low, which ensures more chance to combine with organization .
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2012年第21期2145-2148,共4页
Journal of Third Military Medical University
基金
国家高技术研究发展计划(863计划,2009AA02Z115)
国家重大新药创制课题(2013ZX09103003-001)~~
