2.3 给药途径、方式和剂量选定
Route and method of administration and dose selection
参考rhGH-I药效、长期毒性实验（本实验室操作）及临床拟用剂量，确定大鼠药代动力学、组织分布、粪尿排泄、胆汁排泄以及血浆蛋白结合试验剂量。
Determine the test dose for pharmacokinetics, tissue distribution, waste excretion, biliary excretion and plasma protein binding by making reference to the efficacy and long-term toxicity test (performed by this laboratory) and the planning clinical dose.
参考rhGH-I急性毒性、长期毒性实验（食蟹猴）及临床拟用剂量来确定食蟹猴体内单次、连续给予rhGH-I的药代动力学的剂量。 Determine the dose for in vivo pharmacokinetic studies on single and continuous administration of rhGH-I in cynomolgis monkeys by making reference to acute and long-term toxicity tests (on cynomolgis monkeys) and the planning clinical dose.
华译网上海翻译公司曾经翻译过大量有关给药途径、方式和剂量选定的资料文件。
Beijing Chinese Subtitling Translation Service Agency has translated many technical documents about Route and method of administration and dose selection.
2.4 试验方案 Test Protocol
2.4.1 rhGH-I在食蟹猴体内的药物代谢动力学研究
In vivo pharmacokinetic studies on rhGH-I in cynomolgis monkeys
（1）rhGH-I低、中、高（50、150、500 ug?kg-1）三个剂量单次皮下注射的血药浓度-时间曲线和相关参数；（2）单次皮下注射150 ug?kg-1思真（r-HGH）的血药浓度-时间曲线和相关参数，与rhGH-I进行比较；（3）50 ug?kg-1的rhGH-I每天皮下给药1次，连续4次，比较首次和末次给药后的血药浓度曲线，确定药代动力学行为是否随给药次数而变化；（4）静脉注射150 ug?kg-1 rhGH-I的药代动力学，与皮下注射150 ug?kg-1组相比较计算生物利用度。
Get plasma concentration-time curves and related parameters of single subcutaneous injection of rhGH-I (50, 150 and 500 ug?kg-1, respectively); (2) get plasma concentration-time curve and related parameters of single subcutaneous injection of ug?kg-1 Saizen rhGH-I, comparing them with that of rhGH-I; (3) subcutaneously deliver 50 ug?kg-1 rhGH-I once a day for continuous 4 days and compare the plasma concentration curves after the first and the last administration to see whether pharmacokinetic activities change with injection times; (4) compare the pharmacokinetics of intravenous injection of 150 ug?kg-1 with subcutaneous injection of 150 ug?kg-1 to calculate bioavailability.
2.4.2 单剂量皮下注射125I标记rhGH-I在大鼠体内药物代谢动力学、分布、粪尿与胆汁排泄的研究
In vivo studies on the pharmacokinetics, distribution, waste and bile excretion of 125I tagged rhGH-I after single dose subcutaneous injection
（1）分别采用皮下及静脉注射给予大鼠标记后rhGH-I （125I-rhGH-I）66 ug /只，定时取血，测定放射性浓度；（2）皮下给予大鼠125I-rhGH-I 66 ug /只，分别在1、4、8及24 h活杀动物，取主要脏器，测定脏器的放射性浓度；（3）皮下给予大鼠125I-rhGH-I 66 ug /只，定时分别收集粪、尿，测定粪、尿体积，并测定其放射性，计算粪、尿中各自排出的放射性量；（4）皮下给予大鼠125I-rhGH-I 66 ug /只，定时收集胆汁，测定胆汁中排出的放射性量。
Give per rat tagged 66 ug 125I-rhGH-I through subcutaneous or intravenous way respectively, take blood regularly to determine the radioactive concentration; (2) give per rat subcutaneous 125I-rhGH-I 66 ug, and kill them at 1, 4, 8 and 24h respectively. Take main organs to determine the radioactive concentration; (3) give per rat subcutaneous 125I-rhGH-I 66 ug and take feces and urine regularly for the volume and radioactivity measurement, and calculate the amount of radioactivity in the wastes; (4) give per rat subcutaneous 125I-rhGH-I 66 ug and take the bile regularly to determine the amount of radioactivity in bile.
2.4.3 rhGH-I血浆蛋白结合实验 rhGH-I plasma protein binding test
用分子筛排阻HPLC法检测125I-rhGH-I与大鼠血浆蛋白结合情况，并计算血浆蛋白结合率。
Adopt SHPLC to determine the binding of 125I-rhGH-I and rat plasma protein and calculate plasma protein binding rate.
|
