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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) 无
OBJECTIVE: To study the pharmacokinetics of 125 Ⅰ rhTPO in rats by single-dose 125 I rhGO-125 labeled with recombinant human thrombopoietin. Methods: Sprague-Dawley rats were randomly divided into 3 groups: 125 I rhTPO 0 5, 2 and 8 μg · kg -1, sc, respectively. The radioactivity was measured at different time points and the corresponding plasma concentrations and pharmacokinetic parameters were calculated . Results: Two-chamber model was used to fit the dynamic changes of plasma concentration in rats. The cmax of low, middle and high doses were (0 43 ± 0 0 7), (1 29 ± 0 10) and (44 4 ± 1 17) μg · L -1, respectively; 80 ± 657), (116 ± 0 55) and (84 ± 2 19) h respectively; AUC0 → t were (2443 ± 1 32) and (6293 ± 6 96) , (2 33 80 ± 5 6 2 2) μg · h · L-1, respectively; MRT was (4 1 6 9 ± 3 0 7), (36 0 0 ± 1 6 4), (38 2 2 ± 2 80 ) h and T1 / 2 (β) were (32 30 ± 4 2 0), (2 7 2 7 ± 5 5 4) and (30 0 5 ± 3 81) h, respectively. There was no significant difference in T1 / 2 (β) among the three dose groups (P> 0.05); the difference of tmax and MRT was statistically significant (P <0.05); cmax and AUC0 → t Increased significantly (P <0.01). 12 5 Ⅰ rhTPO 2 μg · kg-1, sc, widely distributed in rats, 96h after excretion of urine and excretion of radioactivity and thyroid iodine up to 80%. Conclusion: The tmax, MRT, cmax and AUC0 → t of 12 5 Ⅰ rhTPO are statistically different among the three dose groups, while T1 / 2 (β)