吲达帕胺片在中国健康受试者中的生物等效性研究  

Bioequivalence study of indapamide tablets in Chinese healthy volunteers

作　　者：张梦琪[1] 刘昀[1] 石峰 朱慧娟 李婷婷[1] 王伟[3] 余琛[1] 贾晶莹[1] ZHANG Meng-qi;LIU Yun;SHI Feng;ZHU Hui-juan;LI Ting-ting;WANG Wei;YU Chen;JIA JING-Ying(Central Laboratory,Shanghai Xuhui Central Hospital,Shanghai Engineering Research Center of Phase I Clinical Research&Quality Consistency Evaluation for Drugs,Shanghai 200031,China;Chongqing Pharmaceutical Co.Ltd.,Chongqing 401121,China;Emergency Department,Shanghai Xuhui Central Hospital,Shanghai 200031,China)

机构地区：[1]上海市徐汇区中心医院中心实验室上海药物Ⅰ期临床暨药物一致性评价工程技术研究中心,上海200031 [2]重庆药友制药有限责任公司,重庆401121 [3]上海市徐汇区中心医院急诊科,上海200031

出　　处：《中国临床药理学杂志》2019年第24期3231-3233,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的 研究吲达帕胺片仿制药与原研药在中国健康受试者中单剂量空腹给药的药代动力学和生物等效性,为临床使用和一致性评价提供依据。方法采用开放、随机、单次口服给药、两制剂、两周期交叉设计,共纳入26名健康受试者,随机分为2组,分别单次空腹口服吲达帕胺片受试制剂与参比制剂2. 5 mg,给药前和给药后按时采集静脉血,以超高效液相色谱-串联质谱(UPLC-MS/MS)法测定全血中吲达帕胺的浓度,随后用SAS9. 4软件计算药代动力学参数,评价生物等效性。结果 吲达帕胺片受试制剂和参比制剂后的主要药动学参数如下:Cmax分别为(114. 28±17. 38)μg·L-1和(96. 27±13. 36)μg·L-1;AUC0-t分别为(1746. 80±297. 16)μg·L-1·h和(1717. 94±77. 49)μg·L-1·h;AUC0-∞分别为(1861. 97±295. 10)μg·L-1·h和(1835. 28±265. 85)μg·L-1·h;Tmax(中位数)分别为2. 0 h和2. 0 h;T1/2分别为(13. 99±1. 71) h和(14. 21±1. 78) h。2种制剂的Cmax、AUC0-t和AUC0-∞经对数转换后90%的置信区间分别为113. 00%~124. 13%,99. 49%~103. 67%,99. 00%~103. 57%。结论 国产吲达帕胺片和进口吲达帕胺片药代动力学生物等效性。Objective To compare the pharmacokinetics and bioequivalence of the domestic and imported tablets of indapamide in Chinese healthy volunteers after single oral administration under fast condition.Methods This was an open,randomized,a single dose,two preparations,two sequences,cross over design.A total of 26 subjects were randomly assigned into two groups and were given a single dose of 2.5 mg indapamide tablets under fasting condition.The blood samples were collected before and after dosing.The concentrations of indapamide in whole blood were determined by an ultra performance liquid chromatographic tandem mass method.The pharmacokinetic parameters were calculated and the bioequivalence was compared by SAS 9.4 software.Results The pharmacokinetic parameters of the domestic and imported tablets were as following:Cmax were(114.28±17.38)μg·L-1 and(96.27±13.36)μg·L-1;AUC0-t were(1746.80±297.16)μg·L-1·h and(1717.94±77.49)μg·L-1·h;AUC0-∞were(1861.97±295.10)μg·L-1·h and(1835.28±265.85)μg·L-1·h;Tmax(Median)were 2.Oh and 2.0 h;T1/2 were(13.99±1.71)h and(14.21±1.78)h.The 90%CIs for Cmax,AUC0-t and AUC0-inf were113.00%-124.13%,99.49%-103.67%and 99.00%-103.57%.Conclusion The results demonstrated that the test products and reference products were bioequivalent.

关 键 词：吲达帕胺 生物等效性 全血 药代动力学 UPLC-MS/MS 

分 类 号：R97[医药卫生—药品]