Huang Kai, Shi Yunfei, Chu Nannan, Que Linling, Ding Ying, Qian Zhenzhong, Qin Wei, Gu Xianghong, Wang Jiakun, Zhang Zhiwei, Xu Jianguo, He Qing
Drug Clinical Trial Institution, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
Wuxi Fuxin Pharmaceutical Research and Development Co., Ltd., Wuxi, China.
Front Pharmacol. 2022 Nov 24;13:1066895. doi: 10.3389/fphar.2022.1066895. eCollection 2022.
This study was performed to investigate the effect of food on the pharmacokinetics (PK) of WXFL10203614 in healthy Chinese subjects. This was a randomized, open-label, single-dose, two-treatment (fed vs fasted), two-period, two-sequence, crossover study. 14 eligible subjects were averagely randomized into 2 sequences and then received 10 mg WXFL10203614 under fasted or fed condition. In each period, the blood samples were collected from 0 h (pre-dose) and serially up to 72 h post-dose, and plasma concentrations were detected using the high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method. The effect of food on the PK profile and safety of WXFL10203614 were assessed. 70 subjects were screened, and 14 subjects (10 male and 4 female) were enrolled and completed the study. Under the fasted condition, WXFL10203614 was absorbed rapidly with a T of 0.98 h. The absorption rate was slower, T delayed by 2.98 h, and the C decreased by 16.3% when WXFL10203614 administered after the high-fat and high-calorie diet, other PK parameters were not affected. The 90% confidence intervals (CIs) for the ratio (fed/fasted) of geometric means of the C, AUC and AUC were 0.73-1.01, 0.90-1.03 and 0.90-1.03, indicating that the high-fat and high-calorie diet might impact the absorption process of WXFL10203614. Although the C was slightly decreased, there was no significant difference in the C under fasted and fed conditions. Thus, it was not considered clinically significant owing to the small magnitude of changes in C. All Treatment-emergent adverse events (TEAEs) were mild and resolved spontaneously without treatment. Food had no clinically relevant effects on drug system exposure of WXFL10203614. It was well tolerated under fasted and fed conditions in healthy Chinese subjects, so WXFL10203614 could be administered orally with or without food. : http://www.chinadrugtrials.org.cn/index.html, identifier CTR20191636.
本研究旨在探讨食物对WXFL10203614在中国健康受试者体内药代动力学（PK）的影响。这是一项随机、开放标签、单剂量、双治疗（进食与空腹）、两周期、两序列的交叉研究。14名符合条件的受试者平均随机分为2个序列，然后在空腹或进食条件下接受10mg WXFL10203614。在每个周期中，于给药前0小时（给药前）及给药后连续至72小时采集血样，采用高效液相色谱-串联质谱（HPLC-MS/MS）法检测血浆浓度。评估食物对WXFL10203614的PK曲线和安全性的影响。共筛选70名受试者，14名受试者（10名男性和4名女性）入组并完成研究。在空腹条件下，WXFL10203614吸收迅速，达峰时间（Tmax）为0.98小时。高脂高热量饮食后服用WXFL10203614时，吸收速率较慢，Tmax延迟2.98小时，Cmax降低16.3%，其他PK参数未受影响。Cmax、AUC0-t和AUC0-∞几何均值的比值（进食/空腹）的90%置信区间（CIs）分别为0.73 - 1.01、0.90 - 1.03和0.90 - 1.03，表明高脂高热量饮食可能影响WXFL10203614的吸收过程。虽然Cmax略有降低，但空腹和进食条件下的Cmax无显著差异。因此，由于Cmax变化幅度较小，未被认为具有临床意义。所有治疗期间出现的不良事件（TEAEs）均为轻度，无需治疗即可自行缓解。食物对WXFL10203614的药物系统暴露无临床相关影响。在中国健康受试者的空腹和进食条件下，其耐受性良好，因此WXFL10203614可以在进食或空腹时口服给药。: http://www.chinadrugtrials.org.cn/index.html，标识符CTR20191636
