厄贝沙坦片在中国健康受试者空腹和餐后状态下人体生物等效性研究  

Bioequivalence of irbesartan tablets in Chinese healthy population under fasting and fed condition

作　　者：梁键 杨丹丹[1] 王逸雅 陈东 欧永玉 阮邹荣[1] 江波[1] LIANG Jian;YANG Dan-dan;WANG Yi-ya;CHEN Dong;OU Yong-yu;RUAN Zou-rong;JIANG Bo(Center of Clinical Pharmacology,2nd Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310009,Zhejiang Province,China;Nanjing Kelitai Pharmaceutical Technology Co.,Ltd.,Nanjing 211100,Jiangsu Province,China;Yangzijiang Pharmaceutical Group Beijing Haiyan Pharmaceutical Co.,Ltd.,Beijing 102206,China)

机构地区：[1]浙江大学医学院附属第二医院临床药理中心,浙江杭州310009 [2]南京科利泰医药科技有限公司,江苏南京211100 [3]扬子江药业集团北京海燕药业有限公司,北京102206

出　　处：《中国临床药理学杂志》2021年第14期1785-1789,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的采用随机、开放、两周期、自身交叉、单次给药试验设计比较厄贝沙坦片与原研产品APROVELⓇ在中国健康人体中的生物利用度,并评价两种制剂的生物等效性。方法分别在空腹和餐后条件下,健康受试者随机交叉单剂量口服厄贝沙坦片受试制剂或参比制剂150 mg。用液相色谱-质谱串联(LC-MS/MS)法测定受试者服药前后不同时间点血浆内药物浓度,用WinNonlin 7.0软件计算主要药代动力学参数,并评价两种制剂的生物等效性。结果共有24例健康受试者入组空腹试验,完成23例。受试者空腹服用厄贝沙坦片受试制剂和参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比的90%置信区间分别为85.49%~97.74%、87.57%~100.50%和86.41%~100.09%;共有24例健康受试者入组并完成餐后试验,受试者餐后服用厄贝沙坦片受试制剂和参比制剂的C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比的90%置信区间分别为99.29%~114.37%、90.27%~98.62%和90.19%~98.18%,均在80.00%~125.00%的生物等效性范围内。结论厄贝沙坦受试制剂和参比制剂Ⓡ在中国健康受试者空腹和餐后服用的情况下等效且安全性良好,临床上可以替换使用。Objective To compare the bioavailability of irbesartan tablets with the original product APROVELⓇ,and to evaluate bioequivalence of two formulations,a randomized,open,two-cycle,self-crossing trial in healthy Chinese population was designed.Methods Under fasting and fed conditions,healthy volunteers were given a single dose of irbesartan test or reference tablets 150 mg.Liquid chromatography-mass spectrometry(LC-MS/MS)method was used to determine drug concentration in the plasma taken at different time points before and after dosing.Pharmacokinetic parameters and the bioequivalence of the two formulations were calculated by WinNonlin 7.0 software.Results A total of 24 healthy volunteers were enrolled in the fasting test and 23 cases were completed.The 90%confidence intervals of the geometric mean ratio of C_(max),AUC_(0-t)and AUC_(0-∞)for the test and reference preparations of irbesartan tablets taken by healthy volunteers under fasting condition were 85.49%-97.74%,87.57%-100.50%and 86.41%-100.09%.A total of 24 healthy volunteers were enrolled and completed the fed test.The 90%confidence intervals of the geometric mean ratio of C_(max),AUC_(0-t)and AUC_(0-∞)for the test and reference preparations of irbesartan tablets taken by healthy volunteers under fed condition were 99.29%-114.37%,90.27%-98.62%and 90.19%-98.18%.All of them were within the range of 80.00%-125.00%.Conclusion The test preparation of irbesartan tablets and the reference preparation are bioequivalent,and they can be used interchangeably clinically.

关 键 词：液相色谱-质谱串联 厄贝沙坦片 药代动力学 生物等效性 

分 类 号：R97[医药卫生—药品]