量化系统药理学模型执行的框架
Victor Sokolov1,2, Kirill Peskov3,4,5, Gabriel Helmlinger6
1M&S Decisions FZ LLC, Dubai, UAE. victor.sokolov@msdecisions.tech.
本章概述了药物开发的定量系统药理 (QSP) 建模工作流程. 它详细介绍了使用普通微分方程的模型开发,校准和模拟方面的挑战.
科学领域:
- 药理学 药理学是指药理学的学科.
- 计算生物学 计算生物学
- 数学建模的数学建模
背景情况:
- 数学模型近似观察到的模式,指导新药的研究和开发,特别是剂量-暴露-反应关系.
- 量化系统药理 (QSP) 模型以机械学方式描述生物系统和治疗干预措施.
研究的目的:
- 提供QSP建模工作流程的全面概述.
- 突出QSP模型开发,校准和解释中的挑战.
- 为新手和经验丰富的QSP建模人员提供资源.
主要方法:
- 使用普通微分方程作为模型构建的中心框架.
- 整合系统的文献审查和选择适当的结构模型方程.
- 执行系统行为分析,模型资格和各种基于模型的模拟.
主要成果:
- QSP模型的开发需要整合现有知识和多样化的数据集,平衡复杂性和不确定性.
- 数据稀缺,特别是在人类受试者层面,使QSP模型校准变得复杂,需要早期敏感性分析.
- 基于模型的预测必须仔细与基础数据和数学方法保持一致.
结论:
- QSP建模工作流包括定义,合格和模拟模型,根据目标进行变化.
- 解决QSP中的挑战需要对生理学和先进的参数估计技术有深入的了解.
- 描述的工作流提供了实施QSP方法的实际指导和资源.
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