使用机器学习增强的阅读交叉方法进行基于生理学的动力学 (PBK) 建模,用于跨物种推断
Yaoxing Wu1, Gabriel Sinclair1, Raghavendhran Avanasi1
1Product Safety, Syngenta Crop Protection LLC, Greensboro NC 27409, USA.
Environment international
|June 10, 2024
概括
这项研究引入了一种新的机器学习方法,用于对杀剂 (如普罗比可纳) 的生理基动力学 (PBK) 建模,通过弥合数据差距和量化物种间差异,实现准确的无动物风险评估.
科学领域:
- 毒理学 毒理学 毒理学
- 计算化学计算化学
- 风险评估 风险评估
背景情况:
- 传统的农业化学风险评估在量化物种间差异方面面临挑战.
- 基于生理学的动力学 (PBK) 建模提供了无动物替代方案,但需要体内数据来验证.
- 数据的有限可用性阻碍了对某些化学品的PBK模型的监管接受.
研究的目的:
- 在缺乏体内药理动力学数据的情况下,为普罗比可纳开发PBK模型.
- 整合阅读交叉方法与机器学习进行客观模拟选择.
- 通过使用动物替代方法完善农业化学品的风险评估策略.
主要方法:
- 开发了PBK模型,使用适合目的的横读方法与层次聚类 (机器学习) 相结合.
- 使用可纳作为源化学物质,使用埃波西可纳,特布可纳和特里亚迪梅作为适用性评估的目标化学物质.
- 整合了构成性安德罗斯坦受体 (CAR) /孕妇X受体 (PXR) 激活,以模拟PBK模型中的代谢自诱导.
主要成果:
- 使用机器学习增强的交叉阅读方法,确定了difenoconazole作为最适合的propiconazole模拟物.
- 使用difenoconazole小鼠模型作为模板构建了一个propiconazole小鼠PBK模型.
- 应用平行图方法来开发普罗皮科纳的老鼠和人类模型,使定量剂量计外推.
结论:
- 综合机器学习和PBK建模方法成功地解决了用于普罗比可纳风险评估的数据缺口.
- 这种方法促进了可重复和客观的模拟选择,推进了无动物安全评估.
- 开发的模型为了解皮可纳剂量测量的物种间差异提供了定量基础.
相关概念视频
01:20Pharmacokinetic Models: Overview
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Pharmacokinetic models utilize mathematical analysis to achieve a detailed quantitative understanding of a drug's life cycle within the body. They are instrumental in simulating a drug's pharmacokinetic parameters, predicting drug concentrations over time, optimizing dosage regimens, linking concentrations with pharmacologic activity, and estimating potential toxicity.
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01:26Pharmacokinetic Models: Comparison and Selection Criterion
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01:06Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
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01:12Analysis of Population Pharmacokinetic Data
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Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...
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01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
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01:21Mechanistic Models: Overview of Compartment Models
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