Makoto Kakitani

Pharmacological effects of recombinant human granulocyte colony-stimulating factor modified by polyethylene glycol on anticancer drug-induced neutropenia in mice

1. To clarify the pharmacological effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) conjugated to polyethylene glycol (PEG), its effects on the number of circulating neutrophils in mice made neutropenic by cyclophosphamide (CPA) or 5-fluorouracil (5-FU) were compared with rhG-CSF lacking PEG. 2. In normal mice, PEG-conjugated rhG-CSF (PEG-rhG-CSF, 10 micrograms protein/kg) induced an increase in neutrophils which lasted for 72 h after injection whereas the effect of rhG-CSF (10 micrograms protein/kg) disappeared by 24 h after injection. 3. In CPA or 5-FU-induced neutropenic mice, PEG-rhG-CSF inhibited neutropenia or accelerated recovery from neutropenia and its potency was higher than that of rhG-CSF. 4. These results indicate that PEG-rhG-CSF has a longer duration of action than rhG-CSF and is more effective in the recovery from neutropenia.