小型分子的生理学基础药理动力学 (PBPK) 建模:我们取得了多少进展?
1Department of Pharmaceutics, University of Washington, United States ni2@u.washington.edu.
Drug metabolism and disposition: the biological fate of chemicals
|February 7, 2024
概括
基于生理学的药理动力学 (PBPK) 模型在药物开发中被广泛使用. 虽然PBPK模型已经进步,以更好地捕捉人类生理学,但模型接受和证明的明确标准往往缺乏.
科学领域:
- 药理动力学和药物开发
- 计算生物学 计算生物学
- 系统药理 系统药理
背景情况:
- 基于生理学的药理动力学 (PBPK) 模型是药物开发和研究的组成部分.
- PBPK的应用正在扩大,以预测药物相互作用,疾病影响和寿命倾向变化.
- 最近的重点包括对怀孕和器官损伤的PBPK建模,并纳入生理变异.
研究的目的:
- 在学术文献中审查PBPK建模应用的现状.
- 要突出PBPK模型复杂性和生理表征的进步.
- 确定需要改进模型质量评估和接受标准的需求.
主要方法:
- 对PBPK建模出版物的文献综述.
- 分析PBPK模型的复杂性和应用趋势.
- 对模型接受标准的报告标准的评估.
主要成果:
- PBPK模型已经推进了复杂的特征,如隔离的肠道和连续的肝脏区.
- 尽管取得了进展,但许多研究缺乏对所选择的模型接受标准和结构的证明.
- 人们越来越意识到需要预先定义的接受标准.
结论:
- PBPK建模是用于药理动力学数据分析和预测的主流工具.
- 在定义和证明模型接受标准方面需要进一步发展.
- 人工智能和机器学习可能会增强PBPK模型评估.
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