%0 Journal Article
%T Pharmacokinetics, tissue distribution, excretion, and antiviral activity of pegylated recombinant human consensus interferon-α variant in monkeys, rats and guinea pigs.
%A Cai Y
%A Zhang Z
%A Fan K
%A Zhang J
%A Shen W
%A Li M
%A Si D
%A Luo H
%A Zeng Y
%A Fu P
%A Liu C
%J Regul Pept
%V 173
%N 1
%D Jan 2012 10
%M 21985916
暂无%R 10.1016/j.regpep.2011.09.008
%X 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.