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Pharmacokinetics of Recombinant Human Granulocyte Colony-stimulating Factor Conjugated to Polyethylene Glycol in Rats

Kirin Brewery Co., Ltd., Pharmaceutical Development Laboratory [H. T., S. M.], Pharmaceutical Laboratory [R. S-I., M. I., K. A.], 2-2 Soujamachi 1-chome, Maebashishi, Gunma 371, Japan

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 µg 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 µg 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 µg 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.

¹ To whom requests for reprints should be addressed, at Kirin Brewery Co., Ltd., Pharmaceutical Development Laboratory, 2-2 Soujamachi 1-chome, Maebashi-shi, Gunma 371, JAPAN

Received 1/28/91. Accepted 5/ 3/91.

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