Pharmacokinetics and bioequivalence of ezetimibe tablet in healthy Chinese subjects under fasting and fed conditions.

IF 0.9 4区医学 Q4 PHARMACOLOGY & PHARMACY

International journal of clinical pharmacology and therapeutics Pub Date : 2024-10-30 DOI:10.5414/CP204642

Guan Liu, Hegui Yan, Baodong Yuan, Gang Li

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引用次数: 0

Abstract

Objective: 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.

Materials and methods: 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.

Results: 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_max, AUC_0-t, and AUC_0-∞ 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_max, AUC_0-t, and AUC_0-∞ 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_max, AUC_0-t, AUC_0-∞ 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.

Conclusion: 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.

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空腹和进食条件下依折麦布片在中国健康受试者中的药代动力学和生物等效性。

研究目的本研究旨在评价依折麦布 10 毫克（试验药物）的药代动力学（PK）参数，并评估其在空腹和进食条件下与中国健康受试者服用的品牌参比产品的生物等效性：在 88 名中国健康受试者中开展了一项单中心、随机、开放标签、四期、两序列、全重复交叉研究。受试者单次口服 10 毫克依折麦布片（试验配方或参考配方）。每次给药之间至少有 14 天的空白期。在规定的时间间隔内采集血样，采用经过验证的超高效液相色谱-串联质谱（UPLC-MS/MS）方法测定血浆中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）的浓度。药代动力学和生物利用度参数通过非室方法估算。同时还记录了不良反应：分别有 40 名和 48 名符合条件的健康受试者参加了空腹和进食研究。在空腹状态下，总依折麦布的Cmax、AUC0-t和AUC0-∞的90%置信区间（CIs）分别为87.17%（81.99 - 92.66%）、95.98%（92.38 - 99.72%）和96.04%（91.37 - 100.95%）。在喂养状态下，总依折麦布的 Cmax、AUC0-t 和 AUC0-∞ 的 90% 置信区间分别为 98.71% (90.11 - 108.13%)、98.32% (94.71 - 102.06%) 和 97.90% (92.68 - 103.42%)。试验制剂和参比制剂在空腹和进食条件下的 Cmax、AUC0-t、AUC0-∞ 几何平均比（GMRs）的 90% CIs 均符合 0.80 - 1.25 的传统生物等效性标准。未发现严重不良反应：结论：在中国受试者空腹和进食条件下，10 毫克依折麦布试验制剂和参比制剂具有生物等效性。两种制剂均显示出良好的安全性和耐受性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International journal of clinical pharmacology and therapeutics 医学-药学

CiteScore

1.70

自引率

12.50%

发文量

116

审稿时长

4-8 weeks

期刊介绍： The International Journal of Clinical Pharmacology and Therapeutics appears monthly and publishes manuscripts containing original material with emphasis on the following topics: Clinical trials, Pharmacoepidemiology - Pharmacovigilance, Pharmacodynamics, Drug disposition and Pharmacokinetics, Quality assurance, Pharmacogenetics, Biotechnological drugs such as cytokines and recombinant antibiotics. Case reports on adverse reactions are also of interest.