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目的考察基于对苯二甲酸聚乙二醇酯-对苯二甲酸丁二醇酯共聚物(PEGT/PBT)的干扰素缓释微球在大鼠体内的药动学行为。方法大鼠皮下注射IFNα-2b注射液及缓释微球后,采集不同时间的血清样品,采用药典三部规定的干扰素活性检测方法细胞病变抑制法检测血清中的药物活性。结果大鼠分别皮下注射干扰素注射液及微球后,血药浓度-时间数据经3P97药动学软件处理后,均符合二室模型,呈一级动力学消除。IFNMs-600和IFNMs-2000微球在大鼠体内的消除半衰期分别是93.76和117.79h,分别是注射液消除半衰期(t1/2β=4.13h)的23.67和28.52倍,血药浓度-时间曲线下面积分别是注射液制剂的3.39和4.49倍。与注射液制剂相比,2组微球制剂的平均滞留时间(MRT)均显著延长(P均小于0.001)。结论基于PEGT/PBT新型材料的干扰素缓释微球具有良好的缓释效果,可以在大鼠体内持续释放半个月左右。
Objective To investigate the pharmacokinetics of interferon sustained-release microspheres based on polyethylene terephthalate-polybutylene terephthalate (PEGT / PBT) in rats. Methods After subcutaneous injection of IFNα-2b injection and sustained-release microspheres, serum samples were collected at different times. The drug activity in serum was detected by the cytopathic inhibitory assay using the interferon activity assay of three pharmacopoeias. Results After the rats were injected subcutaneously with interferon injection and microspheres respectively, the plasma concentration-time data were in accordance with the 2-compartment model after being treated by 3P97 pharmacokinetic software, and the first order kinetics was eliminated. The elimination half-lives of IFNMs-600 and IFNMs-2000 microspheres in rats were 93.76 and 117.79 h, respectively, which were 23.67 and 28.52 times of the elimination half-life of injection (t1 / 2β = 4.13h) The area is 3.39 and 4.49 times that of the injection preparation respectively. The mean residence time (MRT) was significantly longer in both groups (P <0.001) compared to the injection. Conclusion Interferon sustained-release microspheres based on the new PEGT / PBT materials have good sustained-release properties and can be sustained in rats for about half a month.