甲磺酸仑伐替尼胶囊随机开放两周期交叉生物等效性研究  

Research on randomized,open label,double-period,double-cross bioequivalence trial of lenvatinib mesylate capsules

作　　者：宋浩静[1] 邱博[1] 孙雪 郭妮妮 胡义亭[1] 白万军[1] 郭彩会[1] 董占军[1] SONG Hao-jing;QIU Bo;SUN Xue;GUO Ni-ni;HU Yi-ting;BAI Wan-jun;GUO Cai-hui;DONG Zhan-jun(Department of Medicine,Hebei General Hospital,Shijiazhuang 050051,China;CSPC Zhongqi Pharmaceutical Technology(Shijiazhuang)Co.,Ltd.,Shijiazhuang 050000,China)

机构地区：[1]河北省人民医院药学部,石家庄050051 [2]石药集团中奇制药技术(石家庄)有限公司,石家庄050000

出　　处：《中国新药杂志》2022年第4期357-361,共5页Chinese Journal of New Drugs

摘　　要：目的:评价健康受试者空腹和餐后条件下单剂量服用甲磺酸仑伐替尼胶囊受试制剂和参比制剂的生物等效性。方法:采用随机、开放、单剂量、自身交叉设计,LC-MS/MS法测定健康受试者空腹或餐后给药后血浆仑伐替尼浓度,使用Phoenix WinNonlin 8.2软件计算药动学参数,使用SAS 9.4软件进行生物等效性(BE)评价。结果:空腹BE试验:32例健康受试者分别单次空腹服用仑伐替尼受试制剂和参比制剂4 mg后,C_(max),AUC_(0-t)及AUC_(0-∞)的几何均值的比值分别为98.32%,102.57%和102.35%,90%置信区间(90%CI)分别为89.65%~107.82%,97.85%~107.52%和97.73%~107.19%,均落在等效区间80.00%~125.00%范围内。餐后BE试验:32例健康受试者分别高脂餐后服用受试制剂和参比制剂4 mg后,C_(max),AUC_(0-t)及AUC_(0-∞)的几何均值的比值分别为107.92%,102.14%和102.29%,90%CI分别为99.27%~117.34%,99.43%~104.93%和99.69%~104.96%,均落在等效区间80.00%~125.00%范围内。结论:2种制剂在空腹和餐后条件下具有生物等效性。Objective:To evaluate the bioequivalence of test and reference lenvatinib mesylate capsules after single dose administration under fasting and fed conditions in healthy volunteers.Methods:A randomized,open label,single-dose,self-crossover study design was adopted.LC-MS/MS was applied to determine the concentration of lenvatinib in plasma of healthy subjects after administration under fasting or fed condition,while Phoenix WinNonlin 8.2 and SAS 9.4 software were used for pharmacokinetic(PK)parameters calculation and bioequivalence(BE)analysis,respectively.Results:Thirty-two healthy subjects took 4 mg of test preparation and reference preparation under fasting condition.The ratio of the geometric mean of C_(max),AUC_(0-t) and AUC_(0-∞) were 98.32%,102.57%and 102.35%,respectively.The 90%confidence intervals of C_(max),AUC_(0-t) and AUC_(0-∞) were 89.65%~107.82%,97.85%~107.52%and 97.73%~107.19%,respectively.All these data fell within the equivalence interval of 80.00%~125.00%.Thirty-two healthy subjects took 4 mg of test and reference preparations under fed condition.The ratio of the geometric mean of C;,AUC;and AUC;were 107.92%,102.14%and 102.29%,respectively,with 90%confidence intervals of 99.27%~117.34%,99.43%~104.93%and 99.69%~104.96%,respectively,all of which fell within the equivalence range of 80.00%~125.00%.Conclusion:The two preparations are bioequivalent under fasting and fed conditions.

关 键 词：仑伐替尼 生物等效性试验 药动学 

分 类 号：R969.1[医药卫生—药理学]