Pharmacokinetic and pharmacodynamic comparisons between human granulocyte colony-stimulating factor purified from human bladder carcinoma cell line 5637 culture medium and recombinant human granulocyte colony-stimulating factor produced in Escherichia coli

J Pharmacol Exp Ther. 1992 Jul;262(1):439-44.

Abstract

The pharmacokinetics and biological activities of recombinant human granulocyte colony-stimulating factor (hG-CSF) produced in Escherichia coli were compared with those of hG-CSF purified from human bladder carcinoma cell line 5637 culture medium (5637-hG-CSF). Recombinant hG-CSF was biologically active in a bone marrow cell proliferation assay in vitro, with a dose-response curve similar to that of 5637-hG-CSF. The effects of 5637- and recombinant hG-CSF administered via i.v. injection to rats showed similar response patterns of neutrophil counts in peripheral blood. From these results, it is concluded that the O-linked sugar chain of hG-CSF does not contribute to the in vitro and in vivo biological activities. The pharmacokinetics of both forms of hG-CSF in rats were investigated using a sandwich enzyme-linked immunosorbent assay. After i.v. administration, the serum concentration-time curves of 5637- and recombinant hG-CSF declined biexponentially. Total body clearance and steady-state volume of distribution of 5637-hG-CSF were smaller than those for the recombinant form. After s.c. administration, a lower peak serum level, smaller AUC, and lower bioavailability of 5637-hG-CSF were observed compared to recombinant hG-CSF.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Bone Marrow / drug effects
  • Cell Division / drug effects
  • Colony-Stimulating Factors / blood
  • Colony-Stimulating Factors / pharmacokinetics
  • Colony-Stimulating Factors / pharmacology*
  • Escherichia coli / metabolism*
  • Female
  • Hematopoiesis / drug effects
  • Humans
  • Injections, Intravenous
  • Male
  • Mice
  • Mice, Inbred C3H
  • Rats
  • Rats, Inbred Strains
  • Recombinant Proteins / pharmacology
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / metabolism*

Substances

  • Colony-Stimulating Factors
  • Recombinant Proteins