尿酸酶纳米粒在大鼠体内的药代动力学及生物等效性研究  

Study on the pharmacokinetics and bioequivalence of uricase nanoparticles in rats

作　　者：曹鑫 杨兰 钟彩灵 陈云 张景勍[1] CAO Xin;YANG Lan;ZHONG Cai-ling;CHEN Yun;ZHANG Jing-qing(Chongqing Research Center for Pharmaceutical Engineering,College of Pharmacy,Chongqing Medical University,Chongqing 400016,China;Shenzhen Maternal and Child Health Hospital,Shenzhen 518000,Guangdong Province,China)

机构地区：[1]重庆医科大学药学院、重庆高校药物工程研究中心,重庆400016 [2]深圳市妇幼保健院,广东深圳518000

出　　处：《中国临床药理学杂志》2021年第18期2486-2489,共4页The Chinese Journal of Clinical Pharmacology

基　　金：重庆市社会事业与民生保障科技创新专项基金资助项目(cstc2017shmsA130028)。

摘　　要：目的研究尿酸酶(uricase,UR)及其脂质纳米粒(uricase liposome nano-particles,URLP)并分析URLP在雄性大鼠体内的药代动力学过程和生物等效性。方法使用薄膜分散法制备URLP,测定其粒径、ζ电位及包封率。SD大鼠分别静脉给予URLP和UR后,测定各个时间点大鼠血液中尿酸酶(uricase,UR)的活性,并计算URLP的药代动力学参数及生物等效性。结果URLP粒径均一,平均粒径为(286.90±7.19)nm,平均包封为率为(80.01±3.21)%,ζ电位为(-29.63±1.00)mV。URLP和UR经尾静脉注射给药后,主要药代动力学参数AUC0-∞分别为(242.83±78.21)和(210.22±53.37)μg·L^(-1)·h,Cmax分别为(10.61±0.53)和(7.83±1.87)μg·L^(-1),Tmax分别为(0.29±0.18)和(0.17±0.08)h,URLP的相对生物利用度为115.51%。结论将UR制备成URLP后延长了UR在大鼠体内的循环半衰期,提高了UR在大鼠体内的生物利用度,且URLP和游离UR不具有生物等效性。Objective To study uricase(UR)and uricase liposome nanoparticles(URLP),and analyze the pharmacokinetic process and bioequivalence of URLP in male rats.Methods The film dispersion method was used to prepare URLP,and its particle size,zeta potential and encapsulation efficiency were measured.After two groups of SD rats were given URLP and UR intravenously,the activity of uricase in the blood of rats at each time point was measured,and the pharmacokinetic parameters and bioequivalence of URLP were calculated.Results URLP had uniform particle size,the average particle size was(286.90±7.19)nm,the average encapsulation rate was(80.01±3.21)%,and the zeta potential was(-29.63±1.00)mV.After URLP and UR by tail vein injection,the main pharmacokinetic parameters AUC0-∞were(242.83±78.21)and(210.22±53.37)μg·L^(-1)·h-1,Cmax were(10.61±0.53)and(7.83±1.87)μg·L^(-1),Tmax were(0.29±0.18)and(0.17±0.08)h,and the relative bioavailability of URLP was 115.51%.Conclusion URLP prolongs the circulating half-life of UR in rats and improves the bioavailability of UR in rats,and URLP and free UR are not bioequivalent.

关 键 词：尿酸酶 脂质体 药代动力学 生物等效性 高尿酸血症 

分 类 号：R97[医药卫生—药品]