索磷布韦片在中国健康人体中生物等效性和安全性评价

刘广文; 高振月; 于爽; 薛金玲; 梁文忠; 兰静; 杨海淼

doi:10.3969/j.issn.1001-5256.2020.12.010

索磷布韦片在中国健康人体中生物等效性和安全性评价

DOI: 10.3969/j.issn.1001-5256.2020.12.010

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
3. 上海药明康德新药开发有限公司

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 sofosbuvir tablets in the healthy Chinese subjects

Phase I Clinical Trial Laboratory,The Affiliated Hospital of Changchun University of Chinese Medicine
Chia Tai Tianqing Pharmaceutical Group Co.,Ltd.
Shanghai WuX i AppT ec New Drug Development Co.,Ltd.

摘要

摘要:
目的研究索磷布韦片药代动力学特征,对2种制剂的生物等效性和安全性进行评价。方法健康受试志愿者均通过长春中医药大学附属医院临床试验招募报名平台征集,空腹组和餐后组分别在2018年9月18日和9月28日集中进行受试者的筛选体检,体检结果符合纳入标准后入组。空腹组和餐后组各40例健康受试者分别口服索磷布韦片受试试剂和参比试剂索磷布韦片索华迪（SOVALDI,400 mg）,本研究为随机、开放、两序列、四周期、单次给药、完全重复交叉健康人体空腹及餐后状态下生物等效性试验,其中空腹组口服受试试剂和参比试剂各20例,餐后组口服受试试剂和参比试剂各20例。液相串联质谱测定人EDTA-K2血浆中索磷布韦及其主要代谢物GS-331007的含量,检测索磷布韦0 h至服药后8 h共计15个时间点血药浓度;检测GS-331007为0 h至服药后72 h共计16个时间点的血药浓度,采用WinNonlin软件计算药代动力学参数,并进行生物等效性评价。结果受试者空腹状态下口服受试制剂和参比制剂后,以索磷布韦的主要药代动力学参数评价受试制剂与参比制剂的生物等效性,Cmax、AUC0-t、AUC0-inf的几何均值比值...
- 丙型肝炎 /
- 抗病毒药 /
- 索磷布韦 /
- 治疗等效 /
- 串联质谱法
Abstract:
Objective To investigate the pharmacokinetic characteristics of sofosbuvir tablets,and to evaluate the bioequivalence and safety of two preparations. Methods Healthy volunteers were recruited through the platform of clinical trial recruitment in The Affiliated Hospital of Changchun University of Chinese Medicine. Screening physical examination was performed for fasting group on September 18,2018 and for postprandial group on September 28,2018,and the volunteers were enrolled after their physical examination results met the inclusion criteria. The fasting group and the postprandial group,with 40 volunteers in each group,were given oral administration of the test preparation sofosbuvir tablets or the reference preparation sofosbuvir tablets( SOVALDI,400 mg). This was a randomized,open-label,two-sequence,four-cycle,single-dose,and completely repeated cross-over bioequivalence test in the fasting or postprandial state in the healthy population; in the fasting group,20 volunteers each received oral administration of the test preparation and the reference preparation,and in the postprandial group,20 volunteers each received oral administration of the test preparation and the reference preparation. Liquid chromatography-tandem mass spectrometry was used to measure the content of sofosbuvir and its major metabolite GS-331007 in human EDTA-K2 plasma; the plasma concentration of sofosbuvir was measured at 15 time points from 0 hour to 8 hours after administration,and that of GS-331007 was measured at 16 time points from 0 hour to 72 hours after administration. WinNonlin software was used to calculate pharmacokinetic parameters and evaluate bioequivalence. Results After the administration of the test preparation and the reference preparation in the fasting state,when the pharmacokinetic parameters of sofosbuvir was used to evaluate the bioequivalence of the test preparation and the reference preparation,the ratios of the geometric means of Cmax,AUC0-t,and AUC0-infwere 90. 55%,97. 26%,and 94. 62%,respectively; when the pharmacokinetic parameters of GS-331007 was used to evaluate the bioequivalence of the test preparation and the reference preparation,the ratios of the geometric means of Cmax,AUC0-t,and AUC0-infwere 98. 91%,98. 98%,and 99. 46%,respec-tively. All of the above values were within the range of 80. 00%-125. 00%. An analysis of variance was performed after the pharmacokinetic parameters of sofosbuvir Cmax,AUC0-t,and AUC0-infwere transformed by natural logarithm,and the results showed that sequence,cycle,and preparation had no marked influence on Cmax,AUC0-t,and AUC0-inf( all P > 0. 05). Conclusion The test preparation of sofosbuvir tablets is bioequivalent to the reference preparation in the fasting and postprandial states.
- hepatitis C /
- antiviral agents /
- sofosbuvir /
- therapentic equivalency /
- tandem mass spectrometry

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