Shen B, Yang Z, Xu J
Institute of Basic Medical Sciences, Beijing.
Zhonghua Yi Xue Za Zhi. 1996 Sep;76(9):654-7.
To conduct preclinical studies and phase I trial of the recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF).
Pharmacodynamics, pharmacokinetic and toxicology of the rhGM-CSF were studied in animal models, and the safety was also evaluated in humans.
The human bone marrow cells could be stimulated by purified rhGM-CSF to form multilineage colonies (CFU-GM and BFU-E). The rhGM-CSF administered for 7 days to Beagle dogs and monkeys subjected to 60Co r-ray irradiation was shown to induce both rapid and sustained increase in circulating leukocyte counts. Toxicology testing showed that the LD50 (i.v) was over 5000 micrograms/kg, and LD50 (i.p) over 10000 micrograms/kg in mice. Administration of the rhGM-CSF in excess of four times as much as clinical dosages was not associated with severe chronic toxicities. Most injected rhGM-CSF was excreted from urine, and did not accumulate in the body. In the phase I clinical trial, injecting 2.5-7.5 micrograms/day of rhGM-CSF was safe.
It is effective and safe to use rhGM-CSF in the treatment of leukocytopenia.
进行重组人粒细胞巨噬细胞集落刺激因子（rhGM-CSF）的临床前研究和Ⅰ期试验。
在动物模型中研究rhGM-CSF的药效学、药代动力学和毒理学，并在人体中评估其安全性。
纯化的rhGM-CSF可刺激人骨髓细胞形成多谱系集落（CFU-GM和BFU-E）。对接受60Coγ射线照射的比格犬和猴连续7天给予rhGM-CSF，可使循环白细胞计数迅速且持续增加。毒理学试验表明，小鼠静脉注射的半数致死量（LD50）超过5000微克/千克，腹腔注射的LD50超过10000微克/千克。给予超过临床剂量四倍以上的rhGM-CSF未出现严重的慢性毒性。大部分注射的rhGM-CSF经尿液排出，未在体内蓄积。在Ⅰ期临床试验中，每天注射2.5 - 7.5微克的rhGM-CSF是安全的。
rhGM-CSF用于治疗白细胞减少症有效且安全。
