机械数学建模在毒理学中的应用:定量系统毒理学 (QST)
1GSK, Stevenage, UK. kylie.x.beattie@gsk.com.
Handbook of experimental pharmacology
|August 13, 2025
概括
量化系统毒理学 (QST) 通过预测毒性来推进基于模型的药物开发. QST模型整合了机制细节,不良结果途径和安全生物标志物,用于药物发现中的目标和非目标毒性评估.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 计算生物学 计算生物学
背景情况:
- 定量系统毒理学 (QST) 是模型信息化药物开发 (MIDD) 中的一个新兴领域.
- 质量测试技术侧重于通过结合安全评估至关重要的机械细节来预测毒性终点.
- 了解目标和非目标毒性对于药物安全性评估至关重要.
研究的目的:
- 定义和区分量化系统毒理学 (QST) 模型与量化系统药理学 (QSP) 模型.
- 为了说明QST模型在预测目标上和目标之外的毒性方面的应用.
- 审查QST模型在药物发现和开发中的使用环境,目标和影响.
主要方法:
- 将机制细节,包括不良结果途径 (AOPs) 纳入QST模型.
- 超治疗剂量和安全生物标志物的建模,以预测毒性.
- 区分QST模型基于它们对安全相关问题的应用,无论是目标毒性还是目标外毒性.
主要成果:
- QST模型可以从夸张的药理学 (在标上) 和无意标的调制 (在标之外) 预测毒性.
- 评估非目标毒性的QST模型往往适用于模式,并专注于一般毒性机制.
- 清晰地区分QSP和QST模型可能具有挑战性;使用上下文是分类的关键.
结论:
- QST模型是预测药物的毒性在不同发展阶段的有价值的工具.
- 展示了QST应用的例子,用于目标和非目标毒性.
- 质量科学技术领域面临挑战,但在改善药物安全方面具有显著的未来潜力.
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