Pharmacokinetic profile of recombination human insulin-like growth factor binding protein-1 in athymic mice.
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.
Yee
D
D
Department of Medicine/Division of Medical Oncology, University of Texas Health Science Center, San Antonio 78284-7884, USA.
Van Den Berg
C L
CL
Kozelsky
T W
TW
Kuhn
J G
JG
Cox
G N
GN
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000493:pharmacokinetics*; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins / Q000493:pharmacokinetics*
D018970:Insulin-Like Growth Factor Binding Protein 1; D008024:Ligands; D011994:Recombinant Proteins