两种剂型S-1（替加氟/吉美嘧啶/奥替拉西钾）胶囊在中国癌症患者空腹和进食条件下的药代动力学及生物等效性：一项多中心、随机、开放标签、单剂量、双周期交叉研究。
Pharmacokinetics and bioequivalence of two formulations of the S-1 (tegafur/gimeracil/oxonate) capsule in Chinese cancer patients under fasting and fed conditions: a multicenter, randomized, open-label, single-dose, double-cycle crossover study.
作者信息
Lu Junli, Lei Yuyan, Mo Yuanyuan, Wang Xiangping, Liu Wanying, Yan Yu, Yang Hongying, Li Canxia, Huang Lifeng, Shen Qiuxia, Wang Caihong, Chen Jingjie, Chen Lulu, Li Xiaohui
机构信息
Phase Ⅰ Clinical Trial Laboratory, The Second Nanning People's Hospital, Nanning, Guangxi, China.
Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, Hunan, China.
出版信息
Front Pharmacol. 2025 Feb 19;16:1494902. doi: 10.3389/fphar.2025.1494902. eCollection 2025.
OBJECTIVE
S-1, an oral multicomponent capsule containing tegafur, gimeracil, and potassium oxonate, has demonstrated efficacy in various tumor types. This study aimed to assess the pharmacokinetics, bioequivalence (BE), and safety of a newly developed generic S-1 capsule compared to the original brand-name formulation in Chinese cancer patients under fasting and fed conditions.
METHODS
A multicenter, randomized, open-label, single-dose, double-cycle crossover study was conducted in Chinese cancer patients. The study involved 120 subjects, with 60 assigned to the fasting group and another 60 to the fed group. In each study cycle, subjects were randomly assigned toreceive either the reference or test S-1 capsule at a 7-day interval. Blood samples were collected for analysis within 48 h after ingestion. The plasma concentrations of tegafur, 5-fluorouracil, gimeracil, and potassium oxonate were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main pharmacokinetic (PK) parameters were calculated using the non-compartmental approach. BE was assessed through geometric mean ratios (GMRs) between the two formulations and their respective 90% confidence intervals (CIs). The safety of the two formulations was also evaluated.
RESULTS
The pharmacokinetics of the two formulations were similar under both fasting and fed conditions. The 90% CIs of the GMRs for the maximum observed serum concentration (C), AUC, and AUC ratios were observed to lie within the BE acceptance range of 80%-125%. Both formulations of the S-1 capsule exhibited similar adverse events (AEs), primarily including decreased white blood cell count and hypertension. These AEs were generally mild and transient. The safety profiles of the two formulations were found to be good and comparable, with no serious adverse events (SAEs) reported.
CONCLUSION
The newly developed generic S-1 and reference formulations exhibit comparable PK in Chinese cancer patients in the fasting and fed state. The formulations of S-1 showed good tolerability and a similar safety profile.
CLINICAL TRIAL REGISTRATION
http://www.chinadrugtrials.org.cn/index.html, identifier CTR20171562.
目的
S-1是一种含有替加氟、吉美嘧啶和奥替拉西钾的口服多组分胶囊，已在多种肿瘤类型中显示出疗效。本研究旨在评估一种新开发的仿制S-1胶囊与原研品牌制剂相比，在中国癌症患者空腹和进食条件下的药代动力学、生物等效性（BE）和安全性。
方法
在中国癌症患者中进行了一项多中心、随机、开放标签、单剂量、双周期交叉研究。该研究涉及120名受试者，其中60名被分配到空腹组，另外60名被分配到进食组。在每个研究周期中，受试者以7天的间隔随机分配接受参比或受试S-1胶囊。在摄入后48小时内采集血样进行分析。通过液相色谱-串联质谱法（LC-MS/MS）测定替加氟、5-氟尿嘧啶、吉美嘧啶和奥替拉西钾的血浆浓度。使用非房室方法计算主要药代动力学（PK）参数。通过两种制剂之间的几何平均比值（GMR）及其各自的90%置信区间（CI）评估生物等效性。还评估了两种制剂的安全性。
结果
两种制剂在空腹和进食条件下的药代动力学相似。观察到的最大血清浓度（C）、AUC和AUC比值的GMR的90%CI在80%-125%的生物等效性接受范围内。S-1胶囊的两种制剂表现出相似的不良事件（AE），主要包括白细胞计数减少和高血压。这些AE通常为轻度且短暂。发现两种制剂的安全性良好且具有可比性，未报告严重不良事件（SAE）。
结论
新开发的仿制S-1与参比制剂在空腹和进食状态下的中国癌症患者中表现出可比的PK。S-1制剂显示出良好的耐受性和相似的安全性。
临床试验注册
http://www.chinadrugtrials.org.cn/index.html，标识符CTR20171562。
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