盐酸托莫西汀胶囊在中国健康受试者的生物等效性试验  

Bioequivalence study of atomoxetine hydrochloride capsules in Chinese healthy subjects

作　　者：张玉坤 王慧娜 王志国 张志清[1] 李德强[1] 李浩 ZHANG Yu-kun;WANG Hui-na;WANG Zhi-guo;ZHANG Zhi-qing;LI De-qiang;LI Hao(Department of Pharmacy,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China;Shandong Dyne Marine Biopharmaceutical Limited Corporation,Rongcheng 264300,Shandong Province,China;Shanghai Xihua Testing Technology Service Co.,Ltd.,Shanghai 200000,China)

机构地区：[1]河北医科大学第二医院药学部,河北石家庄050000 [2]山东达因海洋生物制药股份有限公司,山东荣成264300 [3]上海熙华检测技术服务有限公司,上海200000

出　　处：《中国临床药理学杂志》2023年第21期3154-3158,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究盐酸托莫西汀胶囊在中国健康人体内的生物等效性。方法空腹和餐后条件下各28例健康受试者,按单剂量、自身交叉设计、双周期口服托莫西汀胶囊受试制剂或参比制剂10 mg,用液相色谱-质谱法测定血浆中托莫西汀的血药浓度,用SAS 9.4软件计算药代动力学参数及相对生物利用度,并判定两制剂是否等效。结果在空腹试验中,盐酸托莫西汀胶囊受试制剂与参比制剂的C_(max)分别为(109.65±36.11)和(122.97±25.74)ng·mL^(-1),AUC_(0-t)分别为(705.38±382.15)和(730.79±386.44)ng·mL^(-1)·h,AUC_(0-∞)分别为(710.94±382.79)和(736.19±388.49)ng·mL^(-1)·h。在餐后试验中,盐酸托莫西汀胶囊受试制剂与参比制剂的C_(max)分别为(85.96±22.04)和(82.67±21.95)ng·mL^(-1),AUC_(0-t)分别为(791.60±583.23)和(786.51±584.77)ng·mL^(-1)·h,AUC_(0-∞)分别为(821.83±692.16)和(819.84±701.94)ng·mL^(-1)·h。在空腹和餐后条件下,托莫西汀的Cmax、AUC_(0-t)、AUC_(0-∞)几何均值比值的90%置信区间均在生物等效性的等效范围要求(80.00%~125.00%)内。结论2种盐酸托莫西汀胶囊在中国健康受试者体内生物等效。Objective To evaluate the bioequivalence of atomoxetine hydrochloride capsules in Chinese healthy volunteers.Methods In the fasting and fed tests,28 healthy subjects were respectively given 10 mg of atomoxetine hydrochloride capsule test preparation or reference preparation by single dose,self-cross design and double cycle oral administration.The plasma concentration of atomoxetine was determined by liquid chromatography-mass spectrometry.The pharmacokinetic parameters and relative bioavailability were calculated by SAS 9.4 software to determine whether the two preparations were equivalent.Results Under fasting state,the C_(max) of atomoxetine hydrochloride capsules test and reference preparations were(109.65±36.11)and(122.97±25.74)ng·mL^(-1),AUC_(0-t) were(705.38±382.15)and(730.79±386.44)ng·mL^(-1)·h,AUC_(0-∞)were(710.94±382.79)and(736.19±388.49)ng·mL^(-1)·h,respectively.Under fed state,the C_(max) of atomoxetine hydrochloride capsules test and reference preparations were(85.96±22.04)and(82.67±21.95)ng·mL^(-1),AUC_(0-t) were(791.60±583.23)and(786.51±584.77)ng·mL^(-1)·h,AUC_(0-∞)were(821.83±692.16)and(819.84±701.94)ng·mL^(-1)·h,respectively.The 90%confidence intervals of the geometric mean ratio of C_(max),AUC_(0-t),AUC_(0-∞)were within the requirements of the equivalent range of bioequivalence(80.00%-125.00%).Conclusion Atomoxetine hydrochloride capsules are bioequivalent in Chinese healthy subjects.

关 键 词：盐酸托莫西汀胶囊 生物等效性 药代动力学 液相色谱-串联质谱法 

分 类 号：R971[医药卫生—药品]