聚乙二醇干扰素α2b在SD大鼠体内的药代动力学特征

Pharmacokinetic Behavior of PEG-IFNα2b in SD Rats

目的研究SD大鼠单次及多次皮下注射聚乙二醇干扰素α2b(PEG-IFNα2b)的药代动力学特征。方法单次皮下注射按18、180、900μg/kg给药;多次皮下注射按180μg/kg,1、4、7d给药;在不同时间点采集血样,ELISA法检测血药浓度,并计算药代动力学参数。结果SD大鼠单次给药的血药浓度-时间曲线呈剂量依赖关系,体内呈一级动力学过程,具有线性动力学特征;多次给药后,未见PEG-IFNα2b的达峰值时间延长及峰浓度升高的现象,曲线下面积(AUC)亦未见增加,末次给药后大鼠的血药浓度曲线呈一室开发模型,半衰期与单次给药半衰期无明显差异,多次皮下给药无蓄积倾向。结论PEG-IFNα2b半衰期比IFNα2b显著延长,使用PEG-IFNα2b可以减少用药频次,并可能提高疗效。

Objective To study the pharmacokinetic behavior of PEG-IFNα2b in SD rats after a single or multiple subcutaneous injections. Methods SD rats were treated with PEG-IFNα2b by a single subcutaneous injection at dosages of 18, 180 and 900 μg/kg or by multiple subcutaneous injections each at a dosage of 180 μg/kg on days 1, 4 and 7 respectively. Blood samples were collected at various time points for determination of drug concentration by ELISA, based on which pharmacokinetic parameters were calculated. Results The drug concentration-time curve of single injection showed that the effect of drug was in a dose-depen- dent mode. The in vivo PEG-IFNα2b showed a first-order kinetic process and a linear dynamic character. However, no prolonged peak time, increased peak concentration of drug or increased AUC was observed after multiple injections. The drug concentration-time curve after the last injection fitted to one compartment open model. The half-life of PEG-IFNα2b administered by multiple injections showed no significant difference with that by a single injection, indicating no drug accumulation tendency. Conclusion PEG-IFNα2b showed a longer half-life as compared with IFNα2b, thus decreased the frequency of iniection and might improve the curative effect.