关键词: 药代动力学, 聚乙二醇化新型集成干扰素, 集成干扰素, 大鼠

Abstract: Objective To characterize the parmacokinetics of a novel pegylated consensus interferon(PEG-IFN-SA) following a single subcutaneous administration to rat, compared with those of non-PEG modified IFN-SA. Methods The rats were randomly assigned into four groups in which the rats were given PEG-IFN-SA at doses of 7, 14 and 28 μg/kg, and IFN-SA at a dose of 7 μg/kg, respectively. The serum concentrations of PEG-IFN-SA and IFN-SA were determined using an enzyme-linked immunosorbent assay(ELISA). The pharmacokinetic parameters were calculated by DAS 3.0 software. Results The rats treated with PEG-IFN-SA following single s.c. administration at doses of 7, 14, and 28 μg/kg, a greater than proportional increase in both the peak concentration(C_max) and the area under the concentration-time curve(AUC) for PEG-IFN-SA was observed with increasing dose, while the rate of clearance decreased. Both the time to reach peak concentration(T_max) and serum elimination half life(t_1/2β) did not display markedly dose-dependence and were relatively consistent in the range of 10~20 h. The pegylated protein exhibited improved pharmacokinetic properties compared to IFN-SA at an identical dose, with a 15-fold increase in t_1/2β, and a 10-fold decrease in serum clearance(CL), as well as a 10-fold increase in Tmax, respectively. In addition, AUC of PEG-IFN-SA was approximately 8-fold greater, while Cmax was approximately half that of IFN-SA. Conclusion These findings demonstrate that pegylation of IFN-SA results in more desirable pharmacokinetic properties, prolonged biological half-life, decreased system clearance, enhanced drug exposure, reduced serum peak-to-trough concentration ratio and increased in vivo duration of antiviral efficacy compared to unmodified IFN-SA.

Key words: pharmacokinetics, pegylated consensus interferon, consensus interferon, rat