^(125)I-TRAIL在大鼠体内的药动学(英文)  

Pharmacokinetics of ^(125) I-tumor necrosis factor-related apoptosis inducing ligand in rats

作　　者：钱隽[1] 刘骁[2] 朱建华[1] 李端[2] 王梁华 周劲松 

机构地区：[1]复旦大学药学院放射药学教研室,上海200032 [2]复旦大学药学院药理学教研室,上海200032 [3]恰尔生物技术有限公司,上海200336

出　　处：《中国临床药学杂志》2005年第3期135-138,共4页Chinese Journal of Clinical Pharmacy

摘　　要：目的用放射性核素示踪技术研究TRAIL在大鼠体内的药动学特性。方法大鼠15只,随机分成3组,分别给予以Iodogen法制备的125ITRAIL1.5、5及15mg·kg-1,iv,于不同时相取血测放射性计数,计算相应的血药浓度并以3P87软件处理计算主要的药动学参数。结果制备了符合药动学研究要求的125ITRAIL,其放化纯度>98%。在大鼠体内均可以二室模型拟合血药浓度的动态变化。低、中、高3个剂量的T1/2(α)分别为(5.69±1.39)、(5.84±1.20)、(6.34±0.74)min;T1/2(β)分别为(46.25±11.96)、(47.61±15.07)、(64.64±8.94)min;AUC0→t分别为(120.80±22.42)、(915.70±409.10)、(3991.00±2193.00)mg·min·L-1。经统计分析,T1/2(β)、MRT、CL(s)在3个剂量组间差异无统计学意义(P>0.05),T1/2(β)在高剂量时明显延长;AUC0→t随着剂量增加而显著增加(P<0.05),但是AUC0→t与剂量的比值在低、中剂量、中剂量和高剂量间差异无统计学意义(P>0.05),而低剂量和高剂量间差异有统计学意义(P<0.05)。125ITRAIL1.5mg·kg-1,iv,在大鼠体内分布广泛。排泄试验显示120h后经尿和粪排泄的放射活性及甲状腺组织富集的碘近82%。结论125ITRAIL在低剂量和中剂量时符合线性动力学特征,到高剂量时逐步向非线性动力学过渡;1.5mg·kg-1,iv,肾脏中放射活?AIM To study the pharmacokinetics of TRAIL in SD rats using radioisotopic tracing method. METHODS Fifteen rats were randomly divided into 3 groups. 125I-TRAIL prepared by iodogen method was injected intravenously with a single dosage of 1.5, 5 and 15 mg·kg -1 respectively. Five rats in each group were collected serum at different time following the dosage using intravenously, respectively. The concentration of TRAIL in serum was determined according to the radioactivity of the samples. The 3P87 pharmacokinetic program was used to calculate main pharmacokinetic parameters. Rats received the dose of  125 I-TRAIL of 1.5 mg·kg -1 in tissue distribution and excretion studies. RESULTS The radiochemical purity of  125 I-TRAIL according with the request of pharmacokinetic research was above 98%. The serum concentration-time curves of TRAIL following single intravenous dosage were fit to a two-compartment model. ThemajorpharmacokineticparametersofTRAIL (1.5 , 5 ,15 mg·kg -1) were T 1/2(α) :(5.69±1.39),(5.84±1.20), (6.34±0.74) min, T 1/2(β) :(46.25±11.96),(47.61±15.07),(64.64±8.94)min, AUC 0→t:(120.80±22.42),(915.70±409.10),(3 991.00±2 193.00)mg·min·L -1,respectively. According to the statistical analysis, there was no statistical difference in T 1/2(β), MRT, CL(s) among the three dosage groups(P>0.05),but AUC 0→t increased with dosage (P<0.05).There was no statistical difference not only between dosage 1.5 and 5 mg·kg -1 but also between dosage 5 and 15 mg·kg -1 (P>0.05),but statistical difference between dosage 1.5 and 15 mg·kg -1 (P<0.05) in the ratio of AUC 0→t vs dosage. T 1/2(β) was elongated in high dosage.  125 I-TRAIL was almost present in all the selected tissues . The excretion studies showed that the cumulative urine and feces excretion amount and the enrichment amount in thyroid arrived at 82% in 120 h. CONCLUSION  125I-TRAIL accords with the linear kinetics in low dosage and medium dosage, and transits step by step from the li

关 键 词：^125I 重组人凋亡素2配体 药动学 

分 类 号：R96[医药卫生—药理学]