Pharmacokinetics of recombinant human granulocyte colony-stimulating factor studied in the rat by a sandwich enzyme-linked immunosorbent assay.
A sandwich enzyme-linked immunosorbent assay for the measurement of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rat serum was developed using anti-rhG-CSF Fab'-horseradish peroxidase conjugate. This assay method measured rhG-CSF in rat serum with greater sensitivity than a bioassay. Also, a good agreement between enzyme-linked immunosorbent assay and bioassay was observed with rat serum samples after administration of rhG-CSF. The pharmacokinetics of rhG-CSF were investigated in male Sprague-Dawley rats using enzyme-linked immunosorbent assay at four different doses from 1 to 100 micrograms/kg. For i.v. administration, the serum rhG-CSF concentration-time curves were best described by a biexponential equation. Over the dose range studied, no changes in volume of distribution were observed. However, a reduction in rhG-CSF clearance and prolongation of half-life (beta) were noted as the dose of rhG-CSF increased. For s.c. administration, a markedly lower serum peak rhG-CSF concentration was observed, but after 2 to 3 hr, rhG-CSF concentration was higher than that following i.v. administration. Administration s.c. also caused nonlinear increases in the serum concentration. Bioavailability after s.c. administration was 0.509 to 0.704.
Pharmaceutical Development Laboratory, Kirin Brewery Co., Ltd., Gunma, Japan.
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Tanaka
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Tokiwa
D000818:Animals; D001681:Biological Assay; D004797:Enzyme-Linked Immunosorbent Assay; D004906:Erythrocyte Count; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor