论文标题
使用经典方案，药物 - 动力模型和多尺度空间肝双胞胎，使用经典方案，使用经典方案，使用经典方案，肝毒性外推到体内乙酰氨基毒素肝毒性外推
In-vitro to in-vivo acetaminophen hepatotoxicity extrapolation using classical schemes, pharmaco-dynamic models and a multiscale spatial-temporal liver twin
论文作者
论文摘要
体内外推的体外是毒理学中的关键挑战。在本文中，我们根据机械模型探讨了对乙酰氨基酚（APAP）的外推策略，比较了经典的同质舱室药物 - 动力学（PD）模型和在细胞分辨率下的多尺度数字双轴模型解决肝微结构。这些模型整合了每个单独的肝细胞中的共有解毒反应。我们研究了两种模型对外推的后果，并表明这些模型的性能要比基于最大药物浓度（CMAX）或药物血液浓度的药物运动曲线（AUC）下的经典外推策略更好。
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.
