Liu Guangwen, Xue Jinling, Wang Yanli, Liu Zhengzhi, Li Xue, Qu Dongmei, Su Zhengjie, Xu Kaibo, Qu Xinyao, Qu Zhaojuan, Sun Linlin, Cao Mingming, Wang Ying, Chen Xuesong, Yu Jing, Liu Lang, Deng Qiaohuan, Zhao Yicheng, Zhang Lixiu, Yang Haimiao
Phase I Clinical Trial Laboratory, Affiliated Hospital to Changchun University of Chinese Medicine, Jilin, China.
Department of Clinical Research Center, Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Jiangsu, China.
J Cancer Res Clin Oncol. 2023 Jun;149(6):2585-2593. doi: 10.1007/s00432-022-04148-1. Epub 2022 Jun 30.
Afatinib is an oral, irreversible ErbB family blocker. It binds covalently to the kinase domains of epidermal growth factor (EGFR), HER2 and HER4, resulting in irreversible inhibition of tyrosine kinase autophosphorylation. Our trial compared the bioequivalence and safety between afatinib produced by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. and Giotrif produced by Boehringer Ingelheim.
Healthy Chinese subjects (N = 36) were randomly divided into two groups at a ratio of 1:1. There was a single dose per period of afatinib and Giotrif. The washout was set as 14 days. Plasma drug concentrations of afatinib and Giotrif were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial.
The geometric mean ratios (GMRs) of C, AUC, and AUC for afatinib and Giotrif were 102.80%, 101.83%, and 101.58%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both drugs showed a good safety profile during the trial.
This study showed that afatinib was bioequivalent to Giotrif in healthy Chinese subjects with well safety.
This trial is registered at the Chinese Clinical Trial website ( http://www.chinadrugtrials.org.cn/index.html # CTR20171160).
阿法替尼是一种口服的不可逆表皮生长因子受体（ErbB）家族阻滞剂。它与表皮生长因子受体（EGFR）、人表皮生长因子受体2（HER2）和人表皮生长因子受体4（HER4）的激酶结构域共价结合，导致酪氨酸激酶自磷酸化的不可逆抑制。我们的试验比较了正大天晴药业集团股份有限公司生产的阿法替尼与勃林格殷格翰公司生产的吉泰瑞之间的生物等效性和安全性。
36名健康中国受试者按1:1比例随机分为两组。每个周期单剂量服用阿法替尼和吉泰瑞。洗脱期设定为14天。采用液相色谱-串联质谱法（LC-MS/MS）分析阿法替尼和吉泰瑞的血浆药物浓度。对主要药代动力学（PK）参数进行统计分析以评估药物生物等效性。此外，我们在整个试验过程中评估了药物的安全性。
阿法替尼和吉泰瑞的Cmax、AUC0-t和AUC0-∞的几何平均比值（GMR）分别为102.80%、101.83%和101.58%。90%置信区间（CI）均在80%-125%范围内，符合生物等效性标准。此外，两种药物在试验期间均显示出良好的安全性。
本研究表明，在健康中国受试者中，阿法替尼与吉泰瑞生物等效且安全性良好。
本试验在中国临床试验网站（http://www.chinadrugtrials.org.cn/index.html # CTR20171160）注册。
