title: Pharmacokinetics, tissue distribution, excretion, and antiviral activity of pegylated recombinant human consensus interferon-α variant in monkeys, rats and guinea pigs.
abstract: The study aims to characterize the pharmacokinetic, tissue distribution, excretion, and antiviral activity properties of a novel pegylated recombinant human consensus interferon-α variant (PEG-IFN-SA) following a single subcutaneous administration to monkeys, rats and guinea pigs. Studies included: (1) pharmacokinetic properties of PEG-IFN-SA and comparison with those of non-pegylated IFN-SA in rhesus monkeys and rats; (2) tissue distribution and urinary, fecal, and biliary excretion patterns of (125)I-PEG-IFN-SA in guinea pigs; and (3) antiviral activity assessment of PEG-IFN-SA in cynomolgus monkeys. The pegylated protein exhibited improved pharmacokinetic properties compared to IFN-SA in both monkeys and rats, with a 12-fold and 15-fold increase in elimination half-life, and a 100-fold and 10-fold decrease in serum clearance, as well as a 2.5-fold and 10-fold increase in the time to reach peak serum concentration, respectively. (125)I-PEG-IFN-SA was found to be distributed to most of the tissues examined and has character of targeting special distribution, and urinary appeared to be a major route for the excretion of PEG-IFN-SA in guinea pigs. Serum sample analysis from PEG-IFN-SA-treated monkeys showed dose-dependent antiviral activity for one week. These findings demonstrate that pegylation of IFN-SA results in more desirable pharmacokinetic properties, enhanced drug exposure and sustained-efficacy of in vivo antiviral action.
authors: Department of Pharmaceutical Engineering, School of Chemical and Technology, Tianjin University, 92 Weijin Road, Tianjin 300072, China.
authors: Yongming
authors: Y
authors: Cai
authors: Zongpeng
authors: Z
authors: Zhang
authors: Kai
authors: K
authors: Fan
authors: Jun
authors: J
authors: Zhang
authors: Wenjin
authors: W
authors: Shen
authors: Ming
authors: M
authors: Li
authors: Duanyun
authors: D
authors: Si
authors: Hua
authors: H
authors: Luo
authors: Yong
authors: Y
authors: Zeng
authors: Peng
authors: P
authors: Fu
authors: Changxiao
authors: C
authors: Liu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001646:Bile / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005243:Feces / Q000737:chemistry; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D016898:Interferon-alpha / Q000493:pharmacokinetics* / Q000494:pharmacology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution; D018116:Vesiculovirus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; C571406:PEG-IFN-SA; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C050739:interferon alfacon-1