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

D. Yee, C. L. Van Den Berg, T. W. Kozelsky, J. G. Kuhn, G. N. Cox

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 μg/mL occurring at 1 hour. The area under the concentration-time curve was 78.32 μg 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.

Original languageEnglish (US)
Pages (from-to)154-157
Number of pages4
JournalBiomedicine and Pharmacotherapy
Volume50
Issue number3-4
DOIs
StatePublished - Jan 1 1996

Keywords

  • insulin-like growth factor
  • insulin-like growth factor binding protein
  • pharmacokinetic

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