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中国临床药理学与治疗学 ›› 2022, Vol. 27 ›› Issue (3): 281-286.doi: 10.12092/j.issn.1009-2501.2022.03.006

• 临床药理学 • 上一篇    下一篇

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

吴娟1,2,王志强1,2,周仁鹏1,2,杨晶晶1,2,秦慧玲1,2,张茜1,2,鲁超1,2,胡伟1,2
  

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

  • 收稿日期:2021-04-25 修回日期:2022-03-15 出版日期:2022-03-26 发布日期:2022-04-11
  • 通讯作者: 胡伟,男,博士(后),教授,主任药师,研究方向:临床药理学。 E-mail: huwei@ahmu.edu.cn
  • 作者简介:吴娟,女,硕士,主管药师,研究方向:临床药理学。 E-mail: 15856395115@163.com
  • 基金资助:
    重大新药创制科技重大专项(2020ZX09201014)

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

WU Juan1,2, WANG Zhiqiang1,2, ZHOU Renpeng1,2, YANG Jingjing1,2, QIN Huiling1,2, ZHANG Qian1,2, LU Chao1,2, HU Wei1,2   

  1. 1Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei 230601, Anhui, China; 2Anhui Provincial Institute of Translational Medicine, Hefei 230601, Anhui, China
  • Received:2021-04-25 Revised:2022-03-15 Online:2022-03-26 Published:2022-04-11

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Cmax、AUC0-t和AUC0-∞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Cmax、AUC0-t和AUC0-∞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Cmax、AUC0-t和AUC0-∞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。

关键词: 索拉非尼, 生物等效性, 药代动力学

Abstract: 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 Cmax, AUC0-t and AUC0-∞ 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 Cmax, AUC0-t and AUC0-∞ 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 Cmax, AUC0-t and AUC0-∞ 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.

Key words: sorafenib, bioequivalence, pharmacokinetics

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