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 language | English (US) |
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Pages (from-to) | 154-157 |
Number of pages | 4 |
Journal | Biomedicine and Pharmacotherapy |
Volume | 50 |
Issue number | 3-4 |
DOIs | |
State | Published - 1996 |
Bibliographical note
Funding Information:This work was supported by NIH grants P01 CA30195 and P30CA54174. The author is a Pew Scholar in the Biomedical Sciences and a recipient of an NIH Reseach Career Development Award.
Keywords
- insulin-like growth factor
- insulin-like growth factor binding protein
- pharmacokinetic