Comparative pharmacokinetics of a tumour-targeting therapy candidate rh-IFNα2a-NGR with rh-IFNα2a administered intravenously in mice and rats

• Published in: Journal of pharmacy and pharmacology 2013-04, Vol.65 (4), p.574-581
• Main Authors: Wang, Xue-Xi, Lu, Li, Song, Chun-Li, Qian, Wei-Na, Zhang, Sheng-Yan, Zhang, Ying-Qi, Wu, Yong-Jie
• Format: Article
• Language: English
• Subjects: Angiogenesis Inhibitors - administration & dosage; Angiogenesis Inhibitors - blood; Angiogenesis Inhibitors - pharmacokinetics; Angiogenesis Inhibitors - urine; Animals; Bile - metabolism; Drug Delivery Systems; Drugs, Investigational - administration & dosage; Drugs, Investigational - metabolism; Drugs, Investigational - pharmacokinetics; Humans; Injections, Intravenous; Interferon-alpha - administration & dosage; Interferon-alpha - genetics; Interferon-alpha - metabolism; Interferon-alpha - pharmacokinetics; Mice; Mice, Inbred Strains; Models, Biological; Neoplasm Transplantation; NGR; Oligopeptides - administration & dosage; Oligopeptides - chemistry; Oligopeptides - genetics; Oligopeptides - metabolism; pharmacokinetic; Plasmacytoma - blood supply; Plasmacytoma - metabolism; Plasmacytoma - pathology; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins - administration & dosage; Recombinant Fusion Proteins - blood; Recombinant Fusion Proteins - pharmacokinetics; Recombinant Fusion Proteins - urine; Recombinant Proteins - administration & dosage; Recombinant Proteins - blood; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Recombinant Proteins - pharmacokinetics; Recombinant Proteins - urine; rh-IFNα2a; targeted therapy; Tissue Distribution; tumour
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12022

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