Pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol in rats.
The pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol (PEG-rhG-CSF) and rhG-CSF were studied in male Sprague-Dawley rats. The serum concentration after i.v. administration at a dose of 100 micrograms protein/kg was investigated by a bioassay. The serum rhG-CSF concentration decreased steadily after injection with a terminal half-life of 1.79 h. The PEG-rhG-CSF concentration after injection decreased much more slowly with a half-life of 7.05 h. The slower disappearance of PEG-rhG-CSF resulted in a greater area under the concentration-time curve. The neutrophil count after 100 micrograms of protein/kg of rhG-CSF administration reached a peak 12 h after injection and returned to the control level 48 h after injection. The neutrophil count after 100 micrograms of protein/kg of PEG-rhG-CSF administration was identical to that of rhG-CSF after 12 h but the highest level was maintained for 24 to 72 h after injection and returned to the control level after 168 h. These data indicated that PEG-rhG-CSF administration exerted a sustained biological effect on peripheral blood neutrophils. It is expected that PEG-rhG-CSF may contribute greatly to human G-CSF treatment because it has a prolonged neutrophil-proliferating activity enabling fewer administrations.
Tanaka
H
H
Kirin Brewery Co., Ltd., Pharmaceutical Development Laboratory, Gunma, Japan.
Satake-Ishikawa
R
R
Ishikawa
M
M
Matsuki
S
S
Asano
K
K
D000818:Animals; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D011092:Polyethylene Glycols