甲苯磺酸索拉非尼片在中国健康受试者的生物等效性研究  

Bioequivalence trial of fasting oral sorafenib tosylate tablets in healthy Chinese subjects

作　　者：吴娟 王志强 周仁鹏 杨晶晶[1,2] 秦慧玲 张茜 鲁超[1,2] 胡伟 WU Juan;WANG Zhiqiang;ZHOU Renpeng;YANG Jingjing;QIN Huiling;ZHANG Qian;LU Chao;HU Wei(Department of Clinical Pharmacology,The Second Hospital of Anhui Medical University,Hefei 230601,Anhui,China;Anhui Provincial Institute of Translational Medicine,Hefei 230601,Anhui,China)

机构地区：[1]安徽医科大学第二附属医院药物临床试验研究中心,安徽合肥230601 [2]安徽省转化医学研究院研究型病房,安徽合肥230601

出　　处：《中国临床药理学与治疗学》2022年第3期281-286,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：重大新药创制科技重大专项 (2020ZX09201014)。

摘　　要：目的:比较单次空腹条件下口服甲苯磺酸索拉非尼片在中国健康受试者体内的药代动力学行为,评价受试试剂(T)和参比试剂(R)的生物等效性。方法:采用单中心、随机、开放、两制剂、三周期、三序列(TRR、RTR、RRT)、部分重复交叉试验设计,试验每周期空腹状态下给药一次(0.2 g),36例健康受试者随机分为3组,每组12例。结果:36例健康受试者(女性9例,平均年龄31岁)入组试验。受试制剂和参比制剂的药代动力学参数C_(max)、AUC_(0-t)和AUC_(0-∞)经自然对数转化后的单侧95%置信区间上限分别为-0.0908、-0.0577、-0.0541,单侧95%置信区间上限均小于0;受试制剂与参比制剂的索拉非尼药代动力学参数C_(max)、AUC_(0-t)和AUC_(0-∞)几何均值比值分别为101.65%、100.12%、99.24%,均在80.00%~125.00%范围内,因此受试制剂和参比制剂索拉非尼的C_(max)、AUC_(0-t)和AUC_(0-∞)在空腹状态下生物等效性成立。结论:受试者空腹单次口服0.2 g甲苯磺酸索拉非尼片安全性和耐受性良好。受试制剂与参比制剂在空腹给药状态下生物等效。AIM:To compare the pharmacokinetic behavior of a single oral sorafenib tosylate tablets in Chinese healthy subjects under fasting conditions and evaluate the bioequivalence of the test reagent(T)and the reference reagent(R).METHODS:A single-center,randomized,open-labeled,two-agent,three-period,three-sequence(TRR,RTR,RRT),and partially repeated crossover trial design was adopted.The trial was administered once per cycle(0.2 g)under fasting conditions.36 healthy subjects were randomly divided into 3 groups,each with 12 cases.RESULTS:Thirty-six healthy subjects(9 females,average age 31 years)were enrolled in the trial.The upper limits of the one-sided 95%confidence interval of the pharmacokinetic parameters C_(max),AUC_(0-t) and AUC_(0-∞)of the test reagent and the reference reagent after natural logarithmic transformation were-0.0908,-0.0577,-0.0541.The one-sided 95%upper limit of the confidence interval was less than 0;the ratios of the geometric mean values of the pharmacokinetic parameters C_(max),AUC_(0-t) and AUC_(0-∞)of sorafenib of the test preparation and the reference preparation were 101.65%,100.12%,and 99.24%,respectively.In the range of 80.00%-125.00%,the bioequivalence of C_(max),AUC_(0-t) and AUC_(0-∞)of the test reagent and the reference reagent sorafenib was established under the fasting state.CONCLUSION:The safety and tolerability of a single oral 0.2 g sorafenib tosylate tablet by subjects under fasting conditions were good.The test reagent and the reference reagent are bioequivalent under fasting administration.

关 键 词：索拉非尼 生物等效性 药代动力学 

分 类 号：R969.1[医药卫生—药理学]