药物诱导的肝损伤从器官到叶片的多尺度建模
Alon Malka-Markovitz1, Stelian Camara Dit Pinto1, Mohammed Cherkaoui1
1Center of Excellence, Long Island University, Brooklyn, NY, USA.
NPJ digital medicine
|June 23, 2025
概括
一个新的计算模型使用患者特定数据模拟药物诱导的肝损伤. 这种人类肝脏虚拟双胞胎准确地预测了乙氨基的毒性和空间异质性,有助于药物开发.
科学领域:
- * 计算机建模和模拟
- * 生物医学工程 * 生物医学工程
- *药理学和毒理学 *药理学和毒理学
背景情况:
- *药物诱导性肝损伤 (DILI) 在药物开发和临床实践中提出了重大挑战.
- * 预测DILI的现有方法往往缺乏捕捉复杂生物过程的精度.
- * 之前的工作建立了一个人肝虚拟双胞胎,需要进一步开发预测能力.
研究的目的:
- * 开发一个多尺度计算流体动力学 (CFD) 框架,用于预测乙氨基诱导的肝损伤.
- * 将患者特定的解剖数据整合到全器官肝脏模拟中.
- * 证明模型在模拟动态血流,药物运输和受伤机制方面的能力.
主要方法:
- *创建一个多尺度的CFD框架,整合患者特定的解剖数据.
- *模拟动态血流,药物运输和肝细胞损伤机制.
- * 血管,叶状和细胞尺度的桥梁,以捕捉空间异质性.
主要成果:
- *精确模拟肝脏内的血液流动动力学.
- *可靠的预测乙氨基诱导的肝细胞损伤.
- * 展示了一个可扩展的框架,用于研究肝脏病理中的空间异质性.
结论:
- * 开发的框架确立了全器官虚拟肝脏模拟的基本原则.
- * 这种方法可以指导治疗开发和临床治疗策略.
- *虚拟双胞胎方法可能会减少对动物模型的依赖,用于临床前药物测试.
相关概念视频
Multicompartment Models: Overview
261
Multicompartment models are mathematical constructs that depict how drugs are distributed and eliminated within the body. They segment the body into several compartments, symbolizing various physiological or anatomical areas connected through drug transfer processes such as absorption, metabolism, distribution, and elimination.
These models offer a more comprehensive representation of drug behavior in the body than one-compartment models. They accommodate the complexity of drug distribution,...
These models offer a more comprehensive representation of drug behavior in the body than one-compartment models. They accommodate the complexity of drug distribution,...
261
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
88
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
88


