Abstract
Objectives:
rh-IFNα2a-NGR is a promising anti-tumor candidate. The aim of present study was to compare pharmacokinetics of rh-IFNα2a-NGR with rh-IFNα2a.
Methods:
Pharmacokinetics and elimination were investigated after intravenous administration to mice and rats. Compared tumor and tissue distribution profiles between rh-IFNα2a-NGR and rh-IFNα2a were illustrated in the tumor transplanted mice of SP2/0 myeloma. Double antibody sandwich ELISA method was used to assess the level of both rh-IFNα2a-NGR and rh-IFNα2a in serum, tissue, bile and urine.
Key findings:
After a single intravenous administration, the pharmacokinetic characters of rh-IFNα2a-NGR and rh-IFNα2a were described using a two-compartment model. No significant differences were observed between the two drugs in pharmacokinetic and elimination data. However, the concentration of rh-IFNα2a-NGR in tumor was 5.34 times and 1.52 times as high as that of rh-IFNα2a at 0.5 h (P < 0.01) and 1 h. In addition, immunohistochemical stain displayed rh-IFNα2a-NGR was predominantly located in tumor vascular tissues.
Conclusions:
rh-IFNα2a-NGR could be an agent for tumor vascular-targeting therapy and these findings provided references for further clinical study.
© 2013 The Authors. JPP © 2013. Royal Pharmaceutical Society.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / administration & dosage
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Angiogenesis Inhibitors / blood
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Angiogenesis Inhibitors / pharmacokinetics*
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Angiogenesis Inhibitors / urine
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Animals
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Bile / metabolism
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Drug Delivery Systems*
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Drugs, Investigational / administration & dosage
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Drugs, Investigational / metabolism
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Drugs, Investigational / pharmacokinetics*
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Humans
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Injections, Intravenous
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Interferon alpha-2
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Interferon-alpha / administration & dosage
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Interferon-alpha / genetics
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Interferon-alpha / metabolism
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Interferon-alpha / pharmacokinetics*
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Mice
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Mice, Inbred Strains
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Models, Biological
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Neoplasm Transplantation
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Oligopeptides / administration & dosage
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Oligopeptides / chemistry
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Oligopeptides / genetics
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Oligopeptides / metabolism*
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Plasmacytoma / blood supply
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Plasmacytoma / metabolism*
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Plasmacytoma / pathology
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / blood
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Recombinant Fusion Proteins / pharmacokinetics*
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Recombinant Fusion Proteins / urine
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / blood
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacokinetics
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Recombinant Proteins / urine
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Tissue Distribution
Substances
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Angiogenesis Inhibitors
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Drugs, Investigational
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Interferon alpha-2
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Interferon-alpha
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NGR peptide
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Oligopeptides
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Recombinant Fusion Proteins
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Recombinant Proteins