重组人干扰素α2b聚乳酸乙醇酸共聚物微球在大鼠体内的药动学研究

目的:考察重组人干扰素α2b聚乳酸乙醇酸共聚物(PLGA)微球在大鼠体内的药动学特征。方法:首先对双抗体夹心酶联免疫吸附法用于大鼠血清中干扰素α2b浓度测定进行了方法学考察,然后给2组大鼠分别肌内注射1MIU重组人干扰素α2b的市售注射用灭菌粉末和PLGA微球,按不同时间点取全血,分离血清,测定血清中的干扰素α2b浓度,用3p97软件计算药动学参数。结果:所建立的浓度测定方法可满足药动学研究的方法学要求;大鼠肌内注射2种制剂后,药动学特征均符合二室模型,tmax、t1/2β、AUC分别为0·72h和1·39h、22·71h和33·32h、21668·72和38655·87pg·mL·h-1。与注射用灭菌粉末相比,微球组的tmax、t1/2β明显延长,AUC值增加。结论:所制干扰素α2bPLGA微球在大鼠体内具有较明显的缓释特征。

Pharmacokinetic Study of Recombinant Human Interferon-alpha-2b PLGA Microspheres in Rats

OBJECTIVE： To study the pharmacokinetis of IFNα2b PLGA microspheres in rats. METHODS： Firstly, the double antibody sandwich -ELISA used for the determination of IFNα2b concentration in diluted serum was subjected to validation. Then, two groups of rats were intramuscularly injected with IFNα2b commercial injectable powder or IFNα2b microspheres, with serum samples of different time were taken for determination of concentration of IFNα2b by ELISA method. Pharmacokinetic parameters were calculated with 3p97 software, RESULTS： ELISA method achieved satisfactory results in determination of the IFNa2b concentration in diluted serum, and it was able to meet the requirements for pharmacokinetic study, The pharmacokinetics in two groups fitted two - compartment model after intramuscular injection of IFNα2b commercial injectable powder or IFNα2b microspheres, tmax, t1/ 2β, AUC were 0,72 h, 22,71 h, 21 668,72 pg · mL· h^-1, respectively in IFNα2b commercial injectable powder group versus 1.39 h, 33.32 h, 38 655.87 pg · mL·h^-1, respectively in IFNα2b microspheres group. Compared with injectable powder group, tmax and t 1/2β were prolonged significantly, and the AUC was increased in microspheres group, CONCLUSION ： The recombinant human IFNα2b PLGA microspheres had obvious sustained - release characteristics in rats.