The effect of food on the pharmacokinetics of Sutetinib maleate capsule, an irreversible EGFR tyrosine kinase inhibitor, in healthy Chinese subjects

IF 3 3区 医学 Q2 ONCOLOGY Investigational New Drugs Pub Date : 2024-04-11 DOI:10.1007/s10637-024-01436-0
Bei Cao, Tingting Ma, Yuqiang Zhang, Lei Huang, Hui Lin, Huanhuan Jiang, Yu Zhao, Yan Geng, Yuanxun Yang, Sumin Cao, Juan Li
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Abstract

Sutetinib is an irreversible inhibitor of epidermal growth factor receptor (EGFR) and showed favorable efficacy and safety in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring nondrug-resistant rare EGFR mutations. To evaluate the potential food effect, eighteen healthy Chinese subjects were enrolled in a single-centre, randomized, open-label, two-sequence, two-period crossover study. Sutetinib was administered as a single oral 100 mg under fasting or fed conditions, and pharmacokinetic sampling was performed following each dose and analysed by a validated liquid chromatography/mass spectrometry method. Safety and tolerability were also evaluated. Food intake slightly decreased maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 to infinity (AUC0 − inf) of sutetinib (geometric least-squares mean [GLSM] ratio, 80.94% and 86.11%; 90% confidence interval [CI], 68.43–95.72 and 75.88–97.73) and its active metabolite sutetinib N-Oxide (GLSM ratio, 75.58% and 84.00%; 90% CI, 65.69–86.95 and 75.42–93.56), respectively. In addition, the time to maximum plasma concentration (Tmax) of both sutetinib and its metabolite has been prolonged by 2 h under fed conditions. A total of 31 adverse events (AEs) occurred during the study, with no serious adverse events (SAE) reported, and no obvious difference was observed between the fasting and fed groups. Our results demonstrated that a high-fat and high-calorie diet caused a significant delay in drug absorption and a marginal reduction in drug exposure. Sutetinib was generally well tolerated in healthy Chinese subjects. (This trial was registered at http://www.chinadrugtrials.org.cn. The registration No. is CTR20201933, and the date of registration is 2020-10-16).

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食物对中国健康受试者服用不可逆表皮生长因子受体酪氨酸激酶抑制剂马来酸舒替尼胶囊药代动力学的影响
舒替尼是表皮生长因子受体(EGFR)的不可逆抑制剂,对携带非耐药罕见EGFR突变的局部晚期或转移性非小细胞肺癌(NSCLC)患者具有良好的疗效和安全性。为了评估潜在的食物效应,18 名中国健康受试者参加了一项单中心、随机、开放标签、两序、两期交叉研究。研究人员在空腹或进食条件下单次口服100毫克舒替替尼,每次服药后进行药代动力学采样,并采用经验证的液相色谱/质谱方法进行分析。此外,还对安全性和耐受性进行了评估。摄入食物会轻微降低苏替尼的最大血浆浓度(Cmax)和从时间0到无穷远的血浆浓度-时间曲线下面积(AUC0 - inf)(几何最小二乘平均值[GLSM]比值,80.94%和86.11%;90%置信区间[CI]分别为68.43-95.72和75.88-97.73)及其活性代谢物苏替尼N-氧化物(GLSM比值分别为75.58%和84.00%;90%置信区间[CI]分别为65.69-86.95和75.42-93.56)。此外,在喂养条件下,苏替尼及其代谢物达到最大血浆浓度(Tmax)的时间延长了2小时。研究期间共发生31例不良事件(AE),无严重不良事件(SAE)报告,空腹组和进食组之间未观察到明显差异。我们的研究结果表明,高脂肪和高热量饮食会显著延迟药物吸收,并略微降低药物暴露量。中国健康受试者对舒替替尼的耐受性普遍良好。(本试验已在 http://www.chinadrugtrials.org.cn 注册。注册号为 CTR20201933,注册日期为 2020-10-16)。
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来源期刊
CiteScore
7.60
自引率
0.00%
发文量
121
审稿时长
1 months
期刊介绍: The development of new anticancer agents is one of the most rapidly changing aspects of cancer research. Investigational New Drugs provides a forum for the rapid dissemination of information on new anticancer agents. The papers published are of interest to the medical chemist, toxicologist, pharmacist, pharmacologist, biostatistician and clinical oncologist. Investigational New Drugs provides the fastest possible publication of new discoveries and results for the whole community of scientists developing anticancer agents.
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