Pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol in rats

• Published in: Cancer research (Chicago, Ill.) Ill.), 1991-07, Vol.51 (14), p.3710-3714
• Main Authors: TANAKA, H, SATAKE-ISHIKAWA, R, ISHIKAWA, M, MATSUKI, S, ASANO, K
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Female; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - pharmacokinetics; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoiesis - drug effects; Male; Medical sciences; Mice; Mice, Inbred C3H; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Rats; Rats, Inbred Strains; Recombinant Proteins - administration & dosage; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - pharmacology
• ISSN: 0008-5472; 1538-7445

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.