Li Yang, Liu Yue, Iwai Megumi, Takeuchi Masato, Song Nan, Li Yuan, Shi Aixin
Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
Astellas Pharma Global Development, Inc, Northbrook, IL, USA.
Drug Des Devel Ther. 2025 Mar 26;19:2243-2252. doi: 10.2147/DDDT.S486562. eCollection 2025.
To evaluate pharmacokinetics (PK) and safety of fezolinetant after single-dose and multiple-dose administration of 15, 30, and 60 mg in healthy Chinese women.
This was a fixed-sequence crossover study in 16 healthy Chinese female subjects, 18-45 years old. All received single doses of fezolinetant 15 mg, 30 mg or 60 mg with a 3-day washout. From Day 10, subjects received multiple doses of 30 mg fezolinetant once-daily for 7 days. PK parameters were obtained during the single- and multiple-dose periods. Safety assessments were based on adverse events, vital signs, and laboratory tests.
Fezolinetant exhibited rapid absorption, with median time of the maximum concentration (t) 1.50 to 1.75 hours after single-dose administration of fezolinetant tablets in the fasted state, followed by a decline in plasma levels, with a mean t of 6.12-7.69 hours at dose levels of 15, 30 and 60 mg. There was a dose-proportional increase in maximum concentration and total exposure for fezolinetant across the doses studied. Mean peak concentration (C) values were 221, 439 and 834 ng/mL, for the 15, 30, and 60 mg doses, respectively. The drug exposure parameters had a low-to-moderate variability (21.1-39.7%). Minimum accumulation was observed after multiple doses. Metabolite ES259564 showed rapid formation following a single dose of fezolinetant, with a median t of 1.50-2.00 hours. Plasma levels then declined, with mean t ranging from 5.72-6.31 hours. Dose-proportional increases in C and AUC were observed following single-doses of fezolinetant. Steady state was achieved on the second day after starting multiple-dose administration. In total, 3 (18.8%) subjects experienced 4 drug-related treatment-emergent adverse events; all mild in severity.
Linear PK was confirmed within the dose range of 15 to 60 mg in healthy Chinese women.
评估非佐利坦在15mg、30mg和60mg单剂量及多剂量给药后，在中国健康女性中的药代动力学（PK）和安全性。
这是一项针对16名年龄在18至45岁的中国健康女性受试者的固定序列交叉研究。所有受试者均接受15mg、30mg或60mg非佐利坦单剂量给药，给药间隔3天。从第10天起，受试者每天接受一次30mg非佐利坦多剂量给药，持续7天。在单剂量和多剂量给药期间获取PK参数。安全性评估基于不良事件、生命体征和实验室检查。
非佐利坦吸收迅速，在禁食状态下单剂量服用非佐利坦片后，最大浓度（t）的中位时间为1.50至1.75小时，随后血浆水平下降，在15mg、30mg和60mg剂量水平下，平均t为6.12 - 7.69小时。在所研究的剂量范围内，非佐利坦的最大浓度和总暴露量呈剂量比例增加。15mg、30mg和60mg剂量的平均峰值浓度（C）值分别为221、439和834ng/mL。药物暴露参数的变异性低至中度（21.1 - 39.7%）。多剂量给药后观察到最小蓄积。代谢物ES259564在单剂量服用非佐利坦后迅速形成，中位t为1.50 - 2.00小时。然后血浆水平下降，平均t为5.72 - 6.31小时。单剂量服用非佐利坦后，观察到C和AUC呈剂量比例增加。多剂量给药开始后第二天达到稳态。总共3名（18.8%）受试者经历了4起与药物相关的治疗中出现的不良事件；严重程度均为轻度。
在中国健康女性中，15至60mg剂量范围内证实了非佐利坦的线性PK。
