[Granulocyte-macrophage colony-stimulating factor (GM-CSF), preclinical and phase I clinical investigations].
OBJECTIVE
To conduct preclinical studies and phase I trial of the recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF).


METHODS
Pharmacodynamics, pharmacokinetic and toxicology of the rhGM-CSF were studied in animal models, and the safety was also evaluated in humans.


RESULTS
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.


CONCLUSIONS
It is effective and safe to use rhGM-CSF in the treatment of leukocytopenia.
Shen
B
B
Institute of Basic Medical Sciences, Beijing.
Yang
Z
Z
Xu
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D004285:Dogs; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D007970:Leukopenia / Q000209:etiology / Q000628:therapy*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D008875:Middle Aged; D009369:Neoplasms / Q000628:therapy*; D011832:Radiation Injuries / Q000628:therapy; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor