阿莫西林颗粒在中国健康人体内的生物等效性研究  

Bioequivalence study of amoxicillin grains in healthy Chinese subjects

作　　者：雷雨燕 卢俊丽[1] 颜羽[1] 陈露露 李晓晖[2,3] 陈维明 夏曼 李超 欧阳冬生 LEI Yu-yan;LU Jun-li;YAN Yu;CHEN Lu-lu;LI Xiao-hui;CHEN Weiming;XIA Man;LI Chao;OUYANG Dong-sheng(Phase I Clinical Trial Laboratory,the Second Nanning People's Hospital,Nanning 530000,Guangxi Province,China;Department of Pharmacology,Xiangya School of Pharmaceutical Science,Central South University,Changsha 410078,Hunan Province,China;Changsha DUXACT Co.,Ld,Changsha 410000,Hunan Province,China;Changsha Phamark Data Technology Co.,Ltd.,Changsha 410000,Hunan Province,China;Hunan Key Laboratory for Bioanalysis of ComplexMatrix Samples,Changsha 410000,Hunan Province,China)

机构地区：[1]南宁市第二人民医院Ⅰ期临床试验研究室,广西南宁530000 [2]中南大学药学院,湖南长沙410078 [3]长沙都正生物科技有限责任公司,湖南长沙410000 [4]长沙砝码科数据科技有限责任公司,湖南长沙410000 [5]复杂基质样本生物分析湖南省重点实验室,湖南长沙410000

出　　处：《中国临床药理学杂志》2023年第18期2684-2688,共5页The Chinese Journal of Clinical Pharmacology

基　　金：湖南省自然科学基金资助项目(2022JJ80100);复杂基质样本生物分析湖南省重点实验室基金资助项目(2017TP1037);湖南省复杂基质样本生物分析国际科技创新合作基地基金资助项目(2019CB1014)。

摘　　要：目的 研究阿莫西林颗粒在中国健康人体内的生物等效性。方法 采用单中心、随机、开放、单剂量、两制剂、两周期、双交叉试验设计。空腹试验和餐后试验中分别入组28例受试者,每周期口服阿莫西林颗粒受试制剂或参比制剂0.5 g。用LC-MS/MS法测定人血浆中阿莫西林的血药浓度,并用Phoenix WinNonlin 8.2软件计算主要药代动力学参数,进行生物等效性评价。结果 空腹试验受试制剂和参比制剂阿莫西林的主要药代动力学参数:C_(max)分别为(11 222.19±2 497.11)和(10 919.47±2 282.44)ng·mL^(-1),AUC_(0-t)分别为(27 238.73±3 324.23)和(26 288.06±2 904.36)h·ng·mL^(-1),AUC_(0-∞)分别为(27 329.87±3 324.57)和(26 373.57±2 902.25)h·ng·mL^(-1),T_(max)均为1.00 h。餐后试验受试制剂和参比制剂阿莫西林的主要药代动力学参数:C_(max)分别为(7 210.34±1 072.25)和(7 140.64±1 175.17)ng·mL^(-1),AUC_(0-t)分别为(27 840.59±3 112.02)和(27 133.23±2 930.17)h·ng·mL^(-1),AUC_(0-∞)分别为(28 041.75±3 168.89)和(27 330.42±3 025.51)h·ng·mL^(-1),T_(max)均为2.50 h。受试制剂与参比制剂C_(max)、AUC_(0-t)、AUC_(0-∞)几何均值比的90%置信区间均在80.00%~125.00%内。结论 2种阿莫西林颗粒在中国健康受试者体内具有生物等效性。Objective To study the bioequivalence of amoxicillin grains in healthy Chinese subjects.Methods A single-center,randomized,open,single-dose,two-cycle,2*2 cross-over trial design was adopted.Under fasting and fedding conditions,28 healthy subjects were given amoxicillin grains test preparation 0.5 g(0.125 g×4 bags)or reference preparation 0.5 g orally.The plasma concentrations of amoxicillin at different time after treatment were detected by LC-MS/MS,and the main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.2 to determine whether the two preparationswere equivalent.ResultsTThe pharmacokinetic parameters of test preparation and reference preparation in fasting state were as folows:Cmaxwere(11222.19±2497.11)and(10919.47±2282.44)ng·mL^(-1);AUC_(0-t)were(27238.73±3324.23)and(26288.06±2904.36)h·ng·mL^(-1);AUC_(0-∞)were(27329.87±3324.57)and(26373.57±2902.25)h·ng·mL^(-1).Both of their T_(max) were 1.00 h.The pharmacokinetic parameters of test preparation and reference preparation in postprandial state were as follows:Cmax were(7210.34±1072.25)and(7140.64±1175.17)ng·mL^(-1);AUC_(0-t) were(27840.59±3112.02)and(27133.23±2930.17)h·ng·mL^(-1);AUC_(0-∞)were(28041.75±3168.89)and(27330.42±3025.51)h·ng mL^(-1).Both of their Tmx were 2.50 h.The 90%confidence intervals of the geometric mean ratios of C_(max),AUC_(0-t) and AUC_(0-∞)of the test preparation and the reference preparation were all completely within 80.00%-125.00%.Conclusion The test and reference preparations of amoxicillin were bioequivalent in Chinese healthy subjects.

关 键 词：阿莫西林颗粒 生物等效性 高效液相色谱-串联质谱 

分 类 号：R969[医药卫生—药理学]