使用经典方案、药效学模型和多尺度时空肝脏孪生模型的体外至体内对乙酰氨基酚肝毒性外推
In-vitro to in-vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmaco-dynamic models and a multiscale spatial-temporal liver twin
摘要：
从体外到体内外推代表了毒理学的关键挑战。在本文中，我们探索外推策略对乙酰氨基酚（APAP）的基础上的机制模型，比较经典的同质房室药效学（PD）模型和多尺度数字孪生模型解决肝脏微结构在细胞分辨率。该模型整合了每个肝细胞中的共识解毒反应。我们研究了两种模型类型的外推的后果，并显示在哪些情况下，这些模型比经典的外推策略，这是基于最大药物浓度（Cmax）或药物血药浓度的药效学曲线（AUC）下的面积更好。
英文摘要：
In vitro to in vivo extrapolation represents a critical challenge in toxicology. In this paper we explore extrapolation strategies for acetaminophen (APAP) based on mechanistic models, comparing classical homogeneous compartment pharmaco-dynamic (PD) models and a multiscale digital twin model resolving liver microarchitecture at cellular resolution. The models integrate consensus detoxification reactions in each individual hepatocyte. We study the consequences of the two model types on the extrapolation and show in which cases these models perform better than the classical extrapolation strategy that is based either on the maximal drug concentration (Cmax) or the area under the pharmaco-kinetic curve (AUC) of the drug blood concentration.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
