恩替卡韦片在中国健康人体中的生物等效性及安全性评价

柳正植; 高振月; 任庆; 霍丹丹; 杨海淼

doi:10.3969/j.issn.1001-5256.2020.12.011

恩替卡韦片在中国健康人体中的生物等效性及安全性评价

DOI: 10.3969/j.issn.1001-5256.2020.12.011

1. 长春中医药大学附属医院Ⅰ期临床试验研究室
2. 正大天晴药业集团股份有限公司临床中心

详细信息

中图分类号: R969
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出版历程
- 收稿日期: 2020-09-08
- 出版日期: 2020-12-20

Bioequivalence and safety of entecavir tablets in healthy Chinese subjects

Institute of Phase I Clinical Trial,The Affiliated Hospital of Changchun University of Chinese Medicine
Clinical Center,Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.

摘要

摘要:
目的评价恩替卡韦仿制药与原研药恩替卡韦片在中国健康受试者中的生物等效性及安全性。方法纳入28例健康受试者,采用随机、开放、两周期、两交叉、空腹状态下的试验设计,两周期分别单次口服受试制剂或参比制剂各0. 5 mg,采用液相色谱串联质谱法（LC-MS/MS）测定服药后72 h内16个不同时间点的血药浓度,计算主要药代动力学参数Cmax、AUC0-t和AUC0-∞评价其生物等效性。采用WinNonlin软件计算药代动力学参数,并进行生物等效性评价。结果空腹状态下口服受试制剂和参比制剂后,主要药动学参数Cmax、AUC0-t和AUC0-∞几何均数的比值分别为98. 18%、101. 97%、103. 07%,90%可信区间分别为91. 36%～105. 50%,98. 32%～105. 74%,96. 30%～110. 32%,均在80. 00%～125. 00%之间。对药代动力学参数Cmax、AUC0-t、AUC0-∞经自然对数转换后,进行方差分析,结果显示空腹状态下给药周期间差异（P<0. p="">0. 05）符合生物等效性判定标准,且在试验过程...
- 乙型肝炎 /
- 恩替卡韦 /
- 治疗等效 /
- 串联质谱法
Abstract:
Objective To investigate the bioequivalence and safety of the generic drug entecavir versus the original drug entecavir tablets in healthy Chinese subjects. Methods A randomized,open,two-cycle,two-cross,fasting trial was designed and performed for 28 healthy subjects,and the subjects were given single oral administration of the test preparation or the reference preparation at a dose of 0. 5 mg in the two cycles,respectively. Liquid chromatography-tandem mass spectrometry was used to measure plasma concentration at 16 different time points within 72 hours after administration,and the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞were calculated to evaluate bioequivalence. WinNonlin software was used to calculate pharmacokinetic parameters and perform bioequivalence evaluation. Results After the oral administration of the test preparation or the reference preparation in the fasting state,the main geometric means( 90% confidence interval) of the main pharmacokinetic parameters Cmax,AUC0-t,and AUC0-∞were 98. 18%( 91. 36%-105. 50%),101. 97%( 98. 32%-105. 74%),and 103. 07%( 96. 30%-110. 32%),respectively,all of which were within the range of 80. 00%-125. 00%.After the pharmacokinetic parameters Cmax,AUC0-t,AUC0-∞were transformed by natural logarithm,the variance analysis was carried out. The P value test results showed that the difference between the dosing weeks( P < 0. 05),the dosing sequence and differences in formulation factors( P > 0. 05). Meet the criteria of bioequivalence. Conclusion The two preparations are bioequivalent and have good safety in healthy Chinese subjects.
- hepatitis B /
- entecavir /
- therapeutic equivalency /
- tandem mass spectrometry

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参考文献(20)

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