盐酸达泊西汀片在中国健康受试者的生物等效性研究  

Bioequivalence study of dapoxetine hydrochloride tablets in Chinese healthy subjects

作　　者：肖功胜 孙宇宏 单娜 党艳妮 惠大永 苗琳琳 刘瑞霞 娄安锋 郭嘉华 刘峰[1,2] XIAO Gong-sheng;SUN Yu-hong;SHAN Na;DANG Yan-ni;HUI Da-yong;MIAO Lin-lin;LIU Rui-xia;LOU An-feng;GUO Jia-hua;LIU Feng(School of Medicine,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,Shaanxi Province,China;Shaanxi Buchang Pharmaceutical Co.,Ltd.,Xianyang 712021,Shaanxi Province,China;Phase I Clinical Laboratory,Zhonghui Cardiovascular Hospital of Henan(Zhengzhou),Zhengzhou 450000,Henan Province,China;Tianjin Hanyi Pharmaceutical Technology Co.,Ltd.,Tianjin 300409,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西咸阳712046 [2]陕西步长制药有限公司,陕西咸阳712021 [3]河南(郑州)中汇心血管病医院Ⅰ期临床试验研究室,河南郑州450000 [4]天津汉一医药科技有限公司,天津300409

出　　处：《中国临床药理学杂志》2024年第21期3153-3157,共5页The Chinese Journal of Clinical Pharmacology

基　　金：陕西省重点研发计划一般基金资助项目(2023-YBSF-533)。

摘　　要：目的评价盐酸达泊西汀片仿制药与原研药在中国健康受试者中单剂量空腹和餐后条件下给药的生物等效性。方法用单中心、随机、开放、单次给药、两制剂、两周期、双交叉试验设计。空腹和餐后试验各入组36例受试者。在空腹或餐后条件下,单次口服盐酸达泊西汀片受试制剂和参比制剂60 mg,用液相色谱串联质谱法测定血浆中达泊西汀的浓度。用Phoenix WinNonlin 8.0软件计算主要药代动力学(PK)参数。结果空腹组的盐酸达泊西汀片受试制剂和参比制剂主要PK参数:达泊西汀Cmax分别为(449.36±203.01)和(432.85±199.75)ng·mL^(-1),AUC_(0-t)分别为(2400.96±1392.58)和(2251.82±1225.84)ng·mL^(-1)·h,AUC_(0-∞)分别为(2529.94±1498.05)和(2371.06±1305.22)ng·mL^(-1)·h。餐后组的盐酸达泊西汀片受试制剂和参比制剂主要PK参数:达泊西汀Cmax分别为(651.29±179.38)和(672.83±249.42)ng·mL^(-1),AUC_(0-t)分别为(3391.27±1358.73)和(3314.53±1360.39)ng·mL^(-1)·h,AUC_(0-∞)分别为(3630.79±1605.89)和(3549.22±1526.61)ng·mL^(-1)·h。在空腹和餐后条件下,受试制剂与参比制剂主要PK参数的90%置信区间均在80.00%~125.00%,表明盐酸达泊西汀片受试制剂和参比制剂在空腹状态和餐后给药时均具有生物等效性。结论盐酸达泊西汀片仿制药与原研药在中国健康受试者体内具有生物等效性。Objective To study the bioequivalence of generic and original dapoxetine hydrochloride tablets in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.Fasting and fed tests were performed on 36 subjects each.Single oral dose 60 mg of test and reference pre parations were taken under fasting and fed conditions,respectively.Plasma concentration of dapoxetine was determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic(PK)parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main PK parameters of the test and reference preparations of dapoxetine tablets in the fasting group were as follows:C_(max)were(449.36±203.01)and(432.85±199.75)ng·mL^(-1);AUC_(0-t)were(2400.96±1392.58)and(2251.82±1225.84)ng·mL-1·h;AUC_(0-∞)were(2529.94±1498.05)and(2371.06±1305.22)ng·mL^(-1)·h.The main PK parameters of the test and reference preparations of dapoxetine tablets in the fed group were as follows:C_(max)were(651.29±179.38)and(672.83±249.42)ng·mL^(-1);AUC_(0-t)were(3391.27±1358.73)and(3314.56±1360.39)ng·mL^(-1)·h;AUC_(0-∞)were(3630.79±1605.89)and(3549.22±1526.61)ng·mL^(-1)·h.Under the fasting and fed conditions,the 90%confidence intervals of the main PK parameters of the test and reference preparations of dapoxetine tablets are 80.00%-125.00%.Conclusion Under the fasting and fed conditions,a single oral dose of generic and original dapoxetine hydrochloride tablets in Chinese healthy adult volunteers showed bioequivalence.

关 键 词：盐酸达泊西汀片 生物利用度 生物等效性 健康受试者 液相色谱-串联质谱 

分 类 号：R97[医药卫生—药品]