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

摘要

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.