Sex differences in the pharmacokinetics of recombinant human granulocyte colony-stimulating factor in the rat.
The pharmacokinetics of recombinant human granulocyte colony-stimulating factor (rhG-CSF) were studied in male and female rats. The serum concentration of rhG-CSF after iv and sc administration to male and female Sprague-Dawley rats at a dose of 5 and 100 micrograms/kg was investigated by a sandwich enzyme-linked immunosorbent assay. After iv administration, AUC and half-lives of rhG-CSF in female rats were smaller than those for male rats. The volume of distribution of rhG-CSF in female rats was not significantly different from that in male rats. After sc administration, AUC, mean residence time, and half-lives of elimination phase in female rats were smaller than those for male rats. The in vitro biological activities of rhG-CSF were investigated using [3H]thymidine uptake assay in cultures of bone marrow cells obtained from male and female rat femur. Female rat bone marrow cells showed a similar dose-response profile to rhG-CSF to that of male rat bone marrow cells. The effect of rhG-CSF administration in rats was a specific activity on the neutrophil lineage with an increase of neutrophils in peripheral blood. The in vivo effects of rhG-CSF after iv and sc administration to male and female rats at 5 and 100 micrograms/kg doses were determined. After 100 micrograms/kg administration, the neutrophil count in female rats was similar to that in male rats in the early period; however, the neutrophil count in female rats was lower than that in male rats 24 hr after administration.(ABSTRACT TRUNCATED AT 250 WORDS)
Tanaka
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Kirin Brewery Co., Ltd., Pharmaceutical Development Laboratory, Gunma, Japan.
Kaneko
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T
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D012727:Sex Characteristics
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor