Pharmacokinetic profile of recombination human insulin-like growth factor binding protein-1 in athymic mice

Biomed Pharmacother. 1996;50(3-4):154-7. doi: 10.1016/0753-3322(96)85290-5.

Abstract

Neutralization of insulin-like growth factor action by insulin-like growth factor binding protein-1 inhibits the in vitro growth of breast cancer cells. We performed this study to determine the pharmacokinetic profile of recombinant human IGFBP-1 (rhIGFBP-1) in athymic mice as a prelude to testing this protein in a human tumor xenograft model. After the subcutaneous injection of 1 mg, rhIGFBP-1 migrating at 29 kDa could be detected by ligand blotting and immunoblotting. Plasma concentrations of rhIGFBP-1 were quantified by immunoassay and demonstrated a half-life was 2.49 hours with the maximal concentration of 43.5 micrograms/mL occurring at 1 hour. The area under the concentration-time curve was 78.32 micrograms x hr/mL. Plasma clearance was 12.77 mL/hr and the mean residence time was 1.96 hours. rhIGFBP-1 was also detected in some tissues and was also cleared rapidly. These results show that high plasma and tissue levels of rhIGFBP-1 can be obtained after subcutaneous injection in athymic mice, however, the short half-life of the protein may limit its therapeutic use.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunoblotting
  • Insulin-Like Growth Factor Binding Protein 1 / pharmacokinetics*
  • Ligands
  • Mice
  • Mice, Nude
  • Recombinant Proteins / pharmacokinetics*

Substances

  • Insulin-Like Growth Factor Binding Protein 1
  • Ligands
  • Recombinant Proteins