title: Comparative Pharmacokinetics, Tissue Distribution, Excretion of Recombinant LiverTargeting Interferon with IFN α2b Administered Intramuscular in Rats.
abstract: Interferon α2b (IFN α2b) is the first cytokine, which has been approved by FDA to treat chronic hepatitis B. However, it has no organ or tissue selectivity effect, and will be rapidly cleared out in the liver after the administration treatment. In our previous study, a novel liver-targeting fusion interferon (IFN-CSP) was constructed by recombining human IFN α2b with a CSP region I-plus peptide. The purpose of this study is to compare pharmacokinetics, tissue distribution, excretion of recombinant liver-targeting interferon IFN-CSP with IFN α2b following intramuscular administration in rats and estimate whether the fusion protein recombinant liver-targeting interferon has liver-targeting effect. Serum, tissue, urinary, fecal, and biliary concentrations of the drug were measured at various time points after administration using ELISA test. The pharmacokinetic character of IFN-CSP and IFNα2b was described using a non-compartmental model after a single intramuscular administration. Our results showed that there were no significant differences between these two drugs in pharmacokinetic and elimination. However, drug concentration of recombinant liver-targeting IFN was higher than IFN α2b in the liver after intramuscular administration in rats at different time points. It was increased in the spleen but not apparently, and decreased in the heart, lung and kidney. In conclusion, compared with traditional IFN 2b, the novel recombinant liver-targeting IFN will be more accumulated in the liver tissue. With this excellent property, IFN-CSP shows a great application prospect in clinical treatment, although further investigation is still needed.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Xuemei
authors.initials: X
authors.lastname: Lu
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Jin
authors.forename: Wenting
authors.initials: W
authors.lastname: Zeng
authors.affiliation: Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, 280 Wai Huan Dong Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, People's Republic of China. zhujiayong1020@163.com.
authors.forename: Jiayong
authors.initials: J
authors.lastname: Zhu