重组人甲状旁腺素（1-34）在大鼠体内的组织分布和排泄

目的：研究重组人甲状旁腺素（1-34）rhPTH（1—34）]在大鼠体内的组织分布和排泄情况，为进一步的临床实验提供参考。方法：用^125I-同位素示踪法结合TCA酸沉淀法测定各主要器官组织的总放射性浓度和酸沉淀部分放射性浓度，获得rhPTH（1-34）的尿粪排泄和胆汁排泄数据。结果：各主要器官组织的总放射性浓度排序由高到低依次为：尿、肾、膀胱、肠内容物、肌肉、血清、肾上腺、空肠、肝、肺脏、卵巢、肠淋巴结、脾、胸腺、心脏、脂肪、睾丸和脑；大鼠皮下注射。^125I-rhPTH（1-34）后，骨骼组织中放射性分布低于血浆，但消除缓慢，血浆浓度4h较15min降低了78％，而骨骼浓度多数仅降低了50％以下；注射后72h，尿、粪分别排出注入放射性量的73．6％±10．9％和3．2％±1．3％，尿、粪合计排出注入放射性量的76．8％±11，4％；注射后12h，胆汁中累积排出注入放射性的6．64％±1．04％。经分子筛排阻HPLC证实，^125I-rhPTH（1-34）不与大鼠的血浆蛋白发生结合。结论：rhPTH（1-34）在泌尿系统中的分布较高，在脂肪和脑中最低，提示药物不易透过血脑屏障；就全身放射性分布而言，在骨骼中分布较高，提示药物具有一定的靶向性；rhPTH（1-34）主要经尿的形式排泄。

Tissue Distribution and Excretion of Recombinant Human Parathyroid Hormone(1-34)in Wistar Rats

Objective： To provide experimental information on the metabolism of recombinant human parathyroid hormone rhPTH（1-34）] in rats necessary for subsequent clinical trials. Methods： ^125I-rhPTH（1-34） was prepared by Iodogen method. Tissue distribution and urinary, fecal, biliary excretion profiles of ^125I-rhPTH（1-34） were demonstrated by TCA precipitation and secHPLC method. Results： In the order of total radioactivity concentration in organs/tissues for ^125I-rhPTH（1-34）, it showed that urine 〉 kidney 〉 bladder 〉 intestinal contents 〉 muscle 〉 serum 〉 adrenal gland 〉 jejunum 〉 liver 〉 lung 〉 ovary 〉 lymph nodes 〉 spleen 〉 thymus 〉 heart 〉 fat 〉 testicle 〉 brain. Approximately 73.6%±10.9% or 3.2%±1.3% of the total administered radioactivity was recovered in urine or feces within 72 h after sc administration, respectively; while 6.64%±1.04% into bile within 12 h after sc administration. It has been convinced that rhPTH（1-34） had no combination with plasma albumin. Conclusion： The results suggested that it was difficult for rhPTH（1-34） to cross the blood-brain barrier. Urinary rout was the dominant excretion one.