[Granulocyte-macrophage colony-stimulating factor (GM-CSF), preclinical and phase I clinical investigations]

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.