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Updated: Jan 9, 2026

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment

Published on: December 3, 2020

使用基于生理学的药理动力学建模和对simvastatin片的虚拟模拟来评估使用母体与代谢物作为生物等价性评估分析物的敏感性

Yi-Hsien Cheng¹, Fang Wu², Miyoung Yoon¹

¹Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.

The AAPS journal

|December 5, 2025

概括

基于生理学的药物动力学建模表明,母药simvastatin在生物等价性评估中通常比其代谢物simvastatin酸更敏感. 然而,当辅料可能影响代谢物暴露时,分析这两者至关重要.

科学领域:

药理动力学和药物新陈代谢
制药科学制药科学
计算建模计算建模

背景情况:

生物等价性 (BE) 评估通常依赖于原始药物,因为与代谢物相比,对配方变化的敏感性更高.
目前关于simvastatin即时释放 (IR) 片的指导建议测量母药和代谢物,而代谢物数据被认为是支持性的.

研究的目的:

评估母药物 (simvastatin) 与代谢物 (simvastatin 酸) 的敏感性,作为使用生理学基础的药物动力学 (PBPK) 建模和虚拟BE (VBE) 模拟进行生物等价性评估的分析物.
探索影响西姆瓦斯塔丁IR片中分析物灵敏性的潜在机制.

主要方法:

开发PBPK模型以模拟健康个体在禁食条件下对simvastatin (SV) 和simvastatin酸 (SVA) 的药物暴露.
进行VBE模拟,以比较SV和SVA在测试和参考产品之间评估BE时的灵敏度.

主要成果:

该PBPK模型准确地捕获了SV和SVA的药理动力学概况,并结合了酶和转运体动力学.
VBE模拟通常表明,原始药物 (SV) 在证明BE方面更敏感.
该研究强调,分析SV和SVA都很重要,特别是当配方助剂可能改变输送活性并随后影响代谢物暴露时.

结论:

虽然原始药物通常对BE更敏感,但在特定情况下,分析代谢物 (SVA) 可能更敏感,从而可能提高对配方效应的评估.
这些发现支持目前针对simvastatin IR片剂的产品特定指南,强调了代谢物数据的价值.

关键词:

代谢物的代谢物.父母父母的父母是什么意思基于生理学的药物动力学建模.西姆瓦斯塔丁是什么意思虚拟的生物等价性

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