机器学习方法的利用用于药物清除预测和人口药理动力学共变量分析
Atul Rawal1, Jiayi Ou1, Hao Zhu2
1Division of Hemostasis, Office of Plasma Protein Therapeutics, Office of Therapeutic Products, Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA), Silver Spring, Maryland, USA.
Clinical and translational science
|September 19, 2025
概括
人工智能和机器学习增强了对药物清除预测和共变量识别的种群药理学分析. 这些先进的方法提供了无偏见的见解,但需要大量的数据来实现最佳性能.
科学领域:
- 药理动力学 药理动力学
- 人工智能的人工智能
- 机器学习 机器学习
背景情况:
- 种群药动力学 (popPK) 分析对于药物剂量建议至关重要.
- 共同变量识别的传统逐步方法可能具有限制性.
- 人工智能/ML为popPK分析提供了先进的替代方案.
研究的目的:
- 展示AI/ML和可解释AI (XAI) 的应用,用于药物清除预测和共变量分析.
- 在不同的数据集和药物类型中比较AI/ML性能.
- 在popPK中探索AI/ML模型的可解释性.
主要方法:
- 使用多个ML模型 (CNN,后勤回归,梯度提升) 进行清除预测.
- 应用夏普利添加剂解释 (SHAP) 用于共同变量识别.
- 测试了不同大小的甲基和雷米芬坦尼尔数据集的模型.
主要成果:
- 实现了高准确度 (R2 > 0.96) 进行甲状腺素清除预测.
- 确定了雷米芬坦尼尔清除的年龄和体重等关键共变量 (R2为0.75).
- 证明AI/ML能够预测清除并无偏见地识别共变量的能力.
结论:
- 通过改进清除预测和共变量发现,AI/ML方法可以显著增强popPK分析.
- 足够大的数据集对于可靠的AI/ML模型性能至关重要.
- 人工智能/ML补充了传统方法,提供了新的见解,同时保持了科学严谨性.
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