一个深度的神经网络:机械混合模型来预测大鼠的药理动力学
Florian Führer1, Andrea Gruber2, Holger Diedam3
1Engineering & Technology, Applied Mathematics, Bayer AG, 51368, Leverkusen, Germany. florian.fuehrer@bayer.com.
从化学结构来预测药物和农业化学品的系统可用性至关重要. 这种改进的混合模型提高了口服和静脉注射的预测准确度,有助于开发.
科学领域:
- 计算化学是一种计算化学.
- 药理动力学 药理动力学
- 药物发现 药物发现
背景情况:
- 系统性可用性预测对于药物和农业化学开发至关重要.
- 准确的预测有助于将资源集中在具有有利动力特征的化合物上.
- 由于复杂的生物和生理相互作用和有限的训练数据,现有的预测模型面临挑战.
研究的目的:
- 改进一种混合模型,用于预测小分子的系统可用性.
- 为了提高口服和静脉注射的预测准确性.
- 扩大模型预测额外的药物动力学终点和处理共变量的能力.
主要方法:
- 改进了之前开发的混合动力模型.
- 对扩展数据集的培训.
- 优化神经网络架构和机械模型参数化的优化.
- 扩展模型以预测新的终点,并纳入性别和剂量形式等共变量.
主要成果:
- 减少了口服总体暴露的中间折叠变化误差,从2.85降至2.35.
- 静脉注射的中间折叠变化误差从1.95降低到1.62.
- 预测新型终点 (例如,24小时暴露) 的能力已被证明,不包括在培训中.
结论:
- 改进的混合模型显著提高了对药物和农业化学品候选物的系统可用性预测的准确性.
- 该模型预测新终点的能力展示了其超出初始培训的稳定性和通用性.
- 这种方法提供了一个有价值的工具,可以优化具有所需药理动力学特性的小分子的开发.
更多相关视频
09:44Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
08:28Microsurgical Skills of Establishing Permanent Jugular Vein Cannulation in Rats for Serial Blood Sampling of Orally Administered Drug
Published on: December 14, 2021
相关概念视频
Mechanistic Models: Overview of Compartment Models
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...
Pharmacokinetic Models: Overview
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
Pharmacokinetic Models: Comparison and Selection Criterion
Physiological models take a detailed approach by considering specific molecular processes. They can predict drug distribution, metabolism, and elimination changes, providing a comprehensive understanding of how drugs interact with the body.
Model Approaches for Pharmacokinetic Data: Compartment Models
Two primary types of compartment models are recognized: mammillary and catenary. The more...
Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
The model approach uses mathematical models to describe changes in drug concentration over time. Pharmacokinetic models help characterize drug behavior in patients, predict drug concentration in the body fluids, calculate optimum dosage regimens, and evaluate the risk of toxicity. However, ensuring that the model fits the experimental data accurately...
