盐酸美金刚缓释胶囊在中国健康受试者的生物等效性研究  

Bioequivalence of memantine hydrochloride sustained-release capsule in Chinese healthy subjects

作　　者：曹莹 王文萍[1] 王华伟[1] 李晓斌[1] 隋鑫[1] 喻明[1] 陈璐 吴秀君[1] 田妍 马然[1] 高雪 张洪超 CAO Ying;WANG Wen-ping;WANG Hua-wei;LI Xiao-bin;SUI Xin;YU Ming;CHEN Lu;WU Xiu-jun;TIAN Yan;MA Ran;GAO Xue;ZHANG Hong-chao(GCP Center Phase Ⅰ Clinical Trial Ward,Affiliated Hospital of Liaoning Universityof Traditional Chinese Medicine,Shenyang 110000,Liaoning Province,China;Jiangsu Tasly Diyi Pharmaceutical Co.,Ltd.Tianjin 300402,China)

机构地区：[1]辽宁中医药大学附属医院GCP中心Ⅰ期临床病房,辽宁沈阳110000 [2]江苏天士力帝益药业有限公司,天津300402

出　　处：《中国临床药理学杂志》2023年第9期1302-1306,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家重点研发计划基金项目资助(2018YFC1311600);辽宁省“兴辽英才计划”基金资助项目(XLYC1802008);辽宁中医药大学附属医院“育苗工程”基金资助项目(YM202001);辽宁中医药大学中药临床药理学科建设基金资助项目。

摘　　要：目的研究空腹及餐后状态下口服两种不同厂家生产的盐酸美金刚缓释胶囊在中国健康受试者体内的生物等效性。方法本研究采用单中心、随机、开放、两周期、双交叉、单次给药的试验设计,空腹组和餐后组各入组28例健康受试者,每周期单次空腹/餐后口服盐酸美金刚缓释胶囊受试制剂或参比制剂28 mg,采用经过验证的LC-MS/MS法测定血浆中美金刚的血药浓度,计算药代动力学参数,进行两种盐酸美金刚缓释胶囊的人体生物等效性及安全性评价。结果空腹组受试制剂和参比制剂的t1/2分别为(66.99±13.32)和(66.79±10.43)h,tmax中位数分别为28.00(14,40)h和30.00(14,40)h,Cmax分别为(31.42±4.47)和(30.69±4.26)ng·mL^(-1),AUC0-t分别为(3592.17±578.74)和(3533.52±516.64)h·ng·mL^(-1),AUC0-∞分别为(3776.91±674.44)和(3712.86±575.83)h·ng·mL^(-1);纳入生物等效性集(BES)的受试者的主要药代动力学参数Cmax、AUC0-t、AUC0-∞的几何均数比值(受试制剂/参比制剂)的90%置信区间统计结果均在可接受的等效范围内,分别为99.58%~106.67%、96.82%~105.54%、96.99%~105.76%。餐后给药组受试制剂和参比制剂的t1/2分别为(71.21±18.14)和(70.99±16.52)h,tmax中位数分别为14.00(10,30)h和14.00(6,34)h,Cmax分别为(37.95±6.37)和(36.99±6.58)ng·mL^(-1),AUC0-t分别为(4063.27±615.23)和(4002.03±693.03)h·ng·mL^(-1),AUC0-∞分别为(4303.71±741.49)和(4242.14±814.13)h·ng·mL^(-1);Cmax、AUC0-t、AUC0-∞的几何均数比值(受试制剂/参比制剂)的90%置信区间统计结果分别为98.86%~105.19%、97.67%~105.95%、97.27%~106.28%。结论盐酸美金刚缓释胶囊受试制剂和参比制剂在空腹和餐后状态下生物等效。Objective To study the bioequivalence of memantine hydrochloride sustained-release capsules produced by two different manufacturers on fasting and fed state in Chinese healthy subjects.Methods In this study,a single-center,randomized,open,double-cycle,double-crossover,single-dose trial design was adopted.Twenty-eight healthy subjects were enrolled in fasting group and fed group respectively,and 28 mg of memantine hydrochloride sustained-release capsule test or reference preparation was taken orally once per cycle.The plasma concentration of memantine hydrochloride was determined by LC-MS/MS method,and the pharmacokinetic parameters were calculated,and the two memantine hydrochloride sustained-release was carried out.Results The tv2 of test preparation and reference preparation in fasting group were(66.99±13.32)and(66.79±10.43)h,respectively;the median of tmax were 28.00(14,40)h and 30.00(14,40)h,and the C,were(31.42±4.47)and(30.69±4.26)ng·mL^(-1),respectively;AUCo^(-1)were max(3592.17±578.74)and(3533.52±516.64)h·ng·mL^(-1),and AUCo-were(3776.91±674.44)and(3712.86±575.83)h·ng·mL^(-1),respectively.The statistical results of 90%confidence intervals of geometric mean ratio(test preparation/reference preparation)of main pharmacokinetic parameters Cmax,AUCo-t and AUCo-αof the subjects included in the bioequivalence set(BES)are within the acceptable equivalence range,which are 99.58%-106.67%and 96.82%-105.54%,respectively.In the fed group,the tiv2 of the test preparation and the reference preparation were(71.21±18.14)and(70.99±16.52)h,respectively;the median of tmax were 14.00(10,30)h and 14.00(6,34)h,and the Cmax were(37.95±6.37)and(36.99±6.58)ng·mL^(-1)respectively;AUCo-t were(4063.27±615.23)and(4002.03±693.03)h·ng·mL^(-1);AUCo-αwere(4303.71±741.49)and(4242.14±814.13)h·ng:mL^(-1),respectively.The statistical of 90%confidence intervals of geometric mean ratio(test preparation/reference preparation)of Cmaxi;AUCo-t and AUCo-were 98.86%-105.19%,97.67%-105.95%and 97.27%-106.28%respectively.Conclu

关 键 词：盐酸美金刚缓释胶囊 健康受试者 生物等效性 液相色谱质谱/质谱联用 

分 类 号：R97[医药卫生—药品]