基于PEGT/PBT新型材料的干扰素缓释微球的药动学研究  

Pharmacokinetics of Microspheres for RhIFNα-2b Based on PEGT/PBT Block Copolymers in Rat

作　　者：曲燕燕[1,2] 张竞[1,2] 苏昕[1] 梅兴国[2] 

机构地区：[1]沈阳药科大学生命科学与生物制药学院,沈阳110016 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国药学杂志》2009年第6期456-459,共4页Chinese Pharmaceutical Journal

摘　　要：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 study the pharmacokinetics in rats after s.c. injeαion of recombinant human interferon α-2b（rhIFNα-2b） micropheres. METHODS The experiment was done by subcutaneous administration in rats and then the samples of blood serum were gatherd at different time. Cytopathic effeα （CPE）method was used to determine the aαivity of rhIFNα-2b in serum. RESULTS The concentration-time curves of rhIFNα-2b microspheres and solution were processed with the pharmacokinetic soft-ware 3P97, both of them were fitted to a two compartment model.Half life and mean residence time（MRT ） of micropheres were significantly prolonged compared with IFNα-2b solution （P〈0.000 1 ） .CONCLUSION The microspheres for rhIFNα-2b based on the PEGT/PBT block copolymer can prolong the MRT in rats and the concentration of IFNα-2b in serum was steady until 15 d.

关 键 词：重组人干扰素Α-2B PEGT/PBT微球 药动学 细胞病变抑制法 

分 类 号：R94[医药卫生—药剂学]