^(125)Ⅰ标记重组人血小板生成素在大鼠体内的药动学

Pharmacokinetics of ^(125)Ⅰ-recombinant human thrombopoietin in rats

目的 :用12 5Ⅰ标记重组人血小板生成素 (12 5Ⅰ rhTPO) ,研究大鼠单剂量皮下注射12 5Ⅰ rhTPO的药动学特性。方法 :将SD大鼠随机分成 3组 ,分别予12 5Ⅰ rhTPO 0 5 ,2及 8μg·kg-1,sc ,于不同时相取血测放射性计数 ,计算相应的血药浓度及药动学参数。结果 :在大鼠体内均可以用二室模型拟合血药浓度的动态变化。低、中、高 3个剂量的cmax分别为 (0 4 3± 0 0 7) ,(1 2 9± 0 10 ) ,(4 4 4± 1 17) μg·L-1;tmax分别为 (16 80± 6 5 7) ,(11 6 0± 0 5 5 ) ,(8 4 0± 2 19)h ;AUC0→t分别为 (2 4 4 3± 1 32 ) ,(6 2 93± 6 96 ) ,(2 33 80± 5 6 2 2 ) μg·h·L-1;MRT分别为 (4 1 6 9± 3 0 7) ,(36 0 0± 1 6 4 ) ,(38 2 2± 2 80 )h ;T1/ 2 (β) 分别为 (32 30±4 2 0 ) ,(2 7 2 7± 5 5 4 ) ,(30 0 5± 3 81)h。经统计分析 ,T1/ 2 (β) 在 3个剂量组间无统计学差异 (P >0 0 5 ) ;tmax,MRT有统计学差异(P <0 0 5 ) ;cmax和AUC0→t随剂量增加而显著增加 (P <0 0 1)。12 5Ⅰ rhTPO 2 μg·kg-1,sc后 ,在大鼠体内分布广泛 ,96h后经尿和粪排泄的放射活性及甲状腺组织富集的碘达 80 %。结论 :12 5Ⅰ rhTPO的tmax,MRT ,cmax,AUC0→t在 3个剂量组间有统计学差异 ,而T1/ 2 (β)

AIM:To investigate the pharmacokinetics of 125Ⅰ-recombinant human thrombopoietin ( 125Ⅰ-rhTPO) in rats receiving single subcutaneous injection. METHODS:Fifteen rats were randomly divided into 3 groups. 125Ⅰ-rhTPO prepared by iodogen method was injected via subcutaneous tissue at the dose of 0 5, 2 and 8 μg·kg -1 respectively. Blood samples were collected at different time after injection, and the drug concentration in plasma and pharmacokinetic parameters of 125Ⅰ-rhTPO were calculated according to the radioactivity of the smaples. RESULTS:The pharmacokinetics of 125Ⅰ-rhTPO following subcutaneous injection with 3 doses (0 5, 2 and 8 μg·kg -1) in rats was in correspondence with two-compartment mode. c max was (0 43±0 07),(1 29±0 10),(4 44±1 17)μg·L -1;t max was(16 80±6 57),(11 60±0 55),(8 40±2 19)h; AUC 0→t was (24 43±1 32),(62 93±6 96),(233 80±56 22)μg·L -1·h;MRT was (41 69±3 07),(36 00±1 64),(38 22±2 80)h;T 1/2(β) was (32 30±4 20),(27 27±5 54),(30 05±3 81)h. According to the statistical analysis, there was no statistical difference of T 1/2(β) among the 3 doses groups, but c max and AUC 0→t increased markedly with doses (P<0 01). The excretion experiment showed that the accumulative excretion of the radio-material and the enrichment of the radio-material in thyroid were approximately 80% in 96 h. CONCLUSION: Among 3 doses groups, the difference of c max and AUC 0→t is highly significant, the difference of t max and MRT is significant, and the difference of T 1/2(β) is insignificant. 125Ⅰ-rhTPO concentration in blood is more than that of tissues and the most radioactive material is excreted through urinary system after 2 μg·kg -1, sc.