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.
Ishikawa
M
M
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan.
Okada
Y
Y
Satake-Ishikawa
R
R
Kakitani
M
M
Kawagishi
M
M
Matsuki
S
S
Kusaka
M
M
Asano
K
K
D000818:Animals; D003520:Cyclophosphamide / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D004353:Drug Evaluation, Preclinical; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008815:Mice, Inbred Strains; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols; D003520:Cyclophosphamide; D005472:Fluorouracil