Yang Yinglin, Kai Jiejing, Lv Duo, Zhou Huili, Yu Yan, Shentu Jianzhong, Wu Guolan
Department of Nursing, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Clinical Pharmacy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Drugs R D. 2025 Aug 22. doi: 10.1007/s40268-025-00521-w.
Flunarizine, a selective calcium channel blocker with vasodilatory and neuroprotective effects, is a mainstay for migraine prophylaxis and vertigo management. This study aimed to compare the bioequivalence, pharmacokinetics, and safety of test and reference flunarizine hydrochloride capsules after a single oral dose under fasting/fed conditions.
A randomized, open-label, two-formulation, single-dose, two-period crossover bioequivalence study was conducted under fasting and fed conditions. Eligible healthy Chinese subjects received a single 5-mg dose of the test or reference flunarizine hydrochloride capsules, followed by a 21-day washout interval between periods. Blood samples were collected up to 36 h post-dose. Pharmacokinetic parameters were calculated using noncompartmental methods, and bioequivalence was assessed via geometric mean ratios of the test/reference for primary pharmacokinetic parameters, along with 90% confidence intervals. Tolerability was evaluated during the entire study period.
Twenty-four volunteers completed the fasting study, while 42 volunteers completed the fed study. The test formulation demonstrated bioequivalence to the marketed formulation, with 90% confidence intervals for geometric mean ratios of peak plasma concentration (fasting: 97.38-106.57%; fed: 92.71-109.58%), area under the curve from time 0 to 36 h (fasting: 98.20-108.09%; fed: 93.79-100.81%), and AUC from time 0 to infinity (fasting: 97.88-107.30%; fed: 93.63-100.53%), all within equivalence limits of 80.00-125.00%. High-fat meals delayed the time to maximum concentration by 2.5 h and increased exposure by 20%. Both the test and reference formulations were well tolerated, and no serious adverse events related to the study drug were reported during the study.
This study confirmed that test and reference flunarizine hydrochloride capsules were bioequivalent under fasting and fed conditions.
ChiCTR1900026713.
氟桂利嗪是一种具有血管舒张和神经保护作用的选择性钙通道阻滞剂，是偏头痛预防和眩晕治疗的主要药物。本研究旨在比较单次口服剂量的受试和参比盐酸氟桂利嗪胶囊在空腹/进食条件下的生物等效性、药代动力学和安全性。
在空腹和进食条件下进行一项随机、开放标签、双制剂、单剂量、两周期交叉生物等效性研究。符合条件的健康中国受试者单次服用5mg受试或参比盐酸氟桂利嗪胶囊，两周期之间有21天的洗脱期。给药后36小时内采集血样。采用非房室方法计算药代动力学参数，并通过主要药代动力学参数的受试/参比几何平均比值及90%置信区间评估生物等效性。在整个研究期间评估耐受性。
24名志愿者完成了空腹研究，42名志愿者完成了进食研究。受试制剂与市售制剂具有生物等效性，峰血浆浓度几何平均比值的90%置信区间（空腹：97.38 - 106.57%；进食：92.71 - 109.58%）、0至36小时曲线下面积（空腹：98.20 - 108.09%；进食：93.79 - 100.81%）以及0至无穷大的AUC（空腹：97.88 - 107.30%；进食：93.63 - 100.53%），均在80.00 - 125.00%的等效性限度内。高脂餐使达峰时间延迟2.5小时，暴露量增加20%。受试和参比制剂耐受性均良好，研究期间未报告与研究药物相关的严重不良事件。
本研究证实受试和参比盐酸氟桂利嗪胶囊在空腹和进食条件下具有生物等效性。
ChiCTR1900026713。
