基于生理学的小分子的药物动力学建模:我们取得了多少进展?
1Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, Washington.
基于生理学的药理动力学 (PBPK) 模型在药物开发方面越来越复杂. 然而,模型接受和证明的明确标准往往缺失,阻碍了科学严谨性.
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) 模型在药物开发和研究中得到广泛使用.
- PBPK的应用正在扩大,以预测药物相互作用,疾病影响和整个生命周期的处置,包括怀孕和器官功能障碍.
- 由于计算能力和多样化的平台,模型复杂性增加了,学术研究推进了生理表征和数学概念.
研究的目的:
- 审查PBPK建模应用程序的当前环境.
- 要突出评估PBPK模型质量和定义接受标准的差距.
- 强调在PBPK模型开发和报告中需要科学理由.
主要方法:
- 关于PBPK建模应用程序和进展的文献综述.
- 对PBPK模型复杂性和生理表征趋势的分析.
- 评估PBPK模型接受标准和理由中的当前做法.
主要成果:
- PBPK模型已经在捕捉人类生理学方面取得了显著的进步,结合了复杂的数学模型,如隔离肠道和连续肝模型.
- 尽管取得了进展,但许多出版物中仍然缺乏预先定义的标准和科学理由来接受PBPK模型.
- 人们越来越意识到需要采用模型接受标准,但实施仍然不一致.
结论:
- 在PBPK建模的持续进步需要在建立强大的模型质量评估和接受标准方面取得平行进展.
- 人工智能和机器学习为增强PBPK模型评估和性能分析提供了潜力.
- 需要在学术界改善PBPK建模科学的培训和标准化,以确保严谨性和可靠性.
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