翻译资源

重组人生长激素注射液（rhGH-I）
Recombinant Human Growth Hormone for Injection (rhGH-I)
非临床药物代谢动力学研究
Non-clinical Pharmacokinetic Studies

1. 研究背景  Research Background
按照我国新生物制品的一般要求，动物需在两种相关动物中提供rhGH-I的：1）相当于人用药物剂量（三个剂量）和途径条件下原形和/或活性代谢物的血浆浓度-时间数据和有关参数；2）药物在体内注射部位及重要器官的分布以及随时间的变化；3）药物经尿、粪和胆汁的排泄；4）药物和血浆蛋白的结合；5）绝对生物利用度的研究。
According to the general requirements for new biological products in our country, the following rhGH-I research data in two relevant animals  should be provided: 1) plasma concentration-time data and related parameters of the prototype and/or the active metabolite under the condition equivalent to the dose (three doses) and route of administration for human; 2) distribution of the drug in injection sites and vital organs and changes over time, 3) excretion of the drug by urine, faeces and bile; 4) combination between the drug and plasma proteins; 5) absolute bioavailability.

2. 关键性技术问题 Key Technical Issues
2.1 动物选择 Animal Selection
根据我国一类新药动物研究的要求，在两种相关（有药效和毒理学效应）动物，进行rhGH-I实验，其中一种必须是大动物，最好是非人灵长类；而分布排泄实验通常选择啮齿类动物。
According to the requirements for animal studies of category 1 new drugs, when rhGH-I study is performed in two relevant animals (with efficacy and toxicological effects), one has to be a large animal and non-human primates are preferred. However, distribution and excretion studies generally prefer rodents.
因此本试验选择大鼠和食蟹猴对rhGH-I进行全面的动物药代动力学研究。
Therefore, rats and cynomolgis monkeys are chosen for this through animal pharmacokinetic study on rhGH-I.

2.2 测定生物体液中rhGH-I的方法
Methods for determination of rhGH-I in animal body fluids
2.2.1 利用免疫定量试剂盒（ELISA法）测定给予rhGH-I后食蟹猴血药浓度变化并计算药代动力学参数。
Make use of quantitative ELISA kits to determine the plasma concentration changes and calculate pharmacokinetic parameters of rhGH-I in cynomolgis monkeys.
2.2.2 采用放射性125I标记- rhGH-I结合分子筛排阻HPLC及γ-计数法，在大鼠体内研究单剂量给予125I-rhGH-I后的药代动力学、组织分布、粪尿排泄、胆汁排泄以及血浆蛋白结合试验。
Adopt radioactive 125I tagged rhGH-I, combining with size exclusive high performance liquid chromatography (SHPLC) and γ-counting to study in vivo pharmacokinetics, tissue distribution, waste excretion, biliary excretion and plasma protein binding in rats after giving single dose 125I-rhGH-I.