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 granulo cyte colony-stimulating factor (rhG-CSF) conjugated to polyethylene gl ycol (PEG), its effects on the number of circulating neutrophils in mi ce made neutropenic by cyclophosphamide (CPA) or 5-fluorouracil (5-FU) were compared with rhG-CSF lacking PEG. 2. In normal mice, PEG-conjug ated rhG-CSF (PEG-rhG-CSF, 10 mu g protein/kg) induced an increase in neutrophils which lasted for 72 h after injection whereas the effect o f rhG-CSF (10 mu g protein/kg) disappeared by 24 h after injection. 3. In CPA or 5-FU-induced neutropenic mice, PEG-rhG-CSF inhibited neutro penia or accelerated recovery from neutropenia and its potency was hig her than that of rhG-CSF. 4. These results indicate that PEG-rhG-CSF h as a longer duration of action than rhG-CSF and is more effective in t he recovery from neutropenia.