Liu Guan, Yan Hegui, Yuan Baodong, Li Gang
Int J Clin Pharmacol Ther. 2025 Jan;63(1):38-46. doi: 10.5414/CP204642.
The purpose of this study is to evaluate the pharmacokinetics (PK) parameters of an ezetimibe 10 mg (test drug) and assess its bioequivalence to the branded reference product in healthy Chinese subjects under fasting and fed conditions.
A single-center, randomized, open-label, four-period, two-sequence, full replicate crossover study was conducted in 88 healthy Chinese subjects under fasting or fed conditions. Subjects received a single oral dose of 10 mg ezetimibe tablet as test or reference formulation. There was a minimum 14-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of free ezetimibe and total ezetimibe (ezetimibe + ezetimibe glucuronide) was determined by a validated ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Pharmacokinetik and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded.
40 and 48 eligible healthy subjects were enrolled in the fasted and fed study. Under fasting state, total ezetimibe with 90% confidence intervals (CIs) of C, AUC, and AUC were 87.17% (81.99 - 92.66%), 95.98% (92.38-99.72%), and 96.04% (91.37 - 100.95%), respectively. Under fed state, total ezetimibe with 90% confidence intervals (CIs) of C, AUC, and AUC were 98.71% (90.11 - 108.13%), 98.32% (94.71 - 102.06%), and 97.90% (92.68 - 103.42%), respectively. The 90% CIs of the ratio of geometric means (GMRs) of C, AUC, AUC of the test and reference formulation in both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80 - 1.25. No severe adverse events were observed.
The test and reference 10-mg ezetimibe tablets were bioequivalent under fasting and fed conditions in Chinese subjects. Both preparations showed good safety and tolerability.
本研究旨在评估10毫克依折麦布（受试药物）的药代动力学（PK）参数，并在空腹和进食条件下，评估其与品牌参比制剂在中国健康受试者中的生物等效性。
在88名空腹或进食状态的中国健康受试者中开展了一项单中心、随机、开放标签、四周期、两序列、完全重复交叉研究。受试者接受单剂量口服10毫克依折麦布片，剂型为受试制剂或参比制剂。每次给药之间至少有14天的洗脱期。在规定的时间间隔采集血样，采用经过验证的超高效液相色谱-串联质谱法（UPLC-MS/MS）测定游离依折麦布和总依折麦布（依折麦布+依折麦布葡萄糖醛酸苷）的血浆浓度。通过非房室方法估算药代动力学和生物利用度参数。同时记录不良事件。
40名和48名符合条件的健康受试者分别纳入空腹和进食状态研究。在空腹状态下，总依折麦布的C、AUC和AUC的90%置信区间（CI）分别为87.17%（81.99 - 92.66%）、95.98%（92.38 - 99.72%）和96.04%（91.37 - 100.95%）。在进食状态下，总依折麦布的C(_max)、AUC(_0-t)和AUC(_0-∞)的90%置信区间（CI）分别为98.71%（90.11 - 108.13%）、98.32%（94.71 - 102.06%）和97.90%（92.68 - 103.42%）。受试制剂与参比制剂在空腹和进食条件下的C(_max)、AUC(_0-t)、AUC(_0-∞)几何均值比（GMR）的90%CI均落在0.80 - 1.25的传统生物等效性标准范围内。未观察到严重不良事件。
受试10毫克依折麦布片与参比制剂在空腹和进食条件下，在中国受试者中具有生物等效性。两种制剂均显示出良好的安全性和耐受性。
