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.