基于计算和人工智能的方法用于药物代谢和运输预测
Balint Dudas1, Maria A Miteva1
1Université Paris Cité, CNRS UMR 8038 CiTCoM, Inserm U1268 MCTR, Paris, France.
Trends in pharmacological sciences
|December 10, 2023
概括
预测药物相互作用 (DDI) 和药物不良反应 (ADR) 对药物开发至关重要. 人工智能 (AI) 方法,包括机器学习 (ML) 和深度学习 (DL),在改善这些预测方面显示出有前途.
科学领域:
- 药理学 药理学是指药理学的学科.
- 计算化学计算化学
- 生物技术是生物技术.
背景情况:
- 药物代谢和运输由药物代谢酶 (DMEs) 和药物运输体 (DTs) 控制,显著影响药物的有效性和安全性.
- 药物相互作用 (DDI) 和药物不良反应 (ADR) 是药物开发中的重大挑战,导致候选药物失败.
- 在发育早期准确预测DDI和ADR对于减轻风险和降低消耗率至关重要.
研究的目的:
- 审查关键药物代谢酶 (DMEs) 和药物输送体 (DTs) 的作用.
- 为预测药物代谢,运输和DDI提供计算方法的概述.
- 突出人工智能 (AI) 在这个领域的进步和潜力.
主要方法:
- 对用于DDI和ADR预测的实验和计算技术的文献综述.
- 专注于人工智能 (AI) 方法,包括机器学习 (ML) 和深度学习 (DL).
- 分析AI在理解药物代谢和运输过程中的应用.
主要成果:
- DMEs和DTs是药物处置的核心,也是DDI预测的关键目标.
- 计算方法,特别是人工智能,为预测复杂的药物相互作用和代谢途径提供了增强的能力.
- 人工智能模型显示了更准确,更早地预测DDI和ADR的潜力.
结论:
- 人工智能包括ML和DL,在预测药物代谢,运输和DDI方面取得了重大进展.
- 改进的预测模型可以通过更早地识别潜在的安全问题来加速药物开发.
- 对人工智能应用的进一步研究对于优化药物安全性和疗效评估至关重要.
更多相关视频
相关概念视频
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
41
Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...
A recent model describes pravastatin's hepatobiliary excretion,...
41
Pharmacokinetic Models: Comparison and Selection Criterion
74
Physiological and compartmental models are valuable tools used in studying biological systems. These models rely on differential equations to maintain mass balance within the system, ensuring an accurate representation of the dynamic processes at play.
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.
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.
74
Model Approaches for Pharmacokinetic Data: Compartment Models
103
Compartmental analysis is a widely adopted approach to characterizing drug pharmacokinetics. It uses compartment models that conceptualize the body as a collection of reversibly communicating compartments, each representing a group of tissues exhibiting similar drug distribution characteristics. The movement rate of the drug between these compartments is typically described by first-order kinetics.
Two primary types of compartment models are recognized: mammillary and catenary. The more...
Two primary types of compartment models are recognized: mammillary and catenary. The more...
103
Analysis Methods of Pharmacokinetic Data: Model and Model-Independent Approaches
134
Drug disposition in the body is a complex process and can be studied using two major approaches: the model and the 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...
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...
134
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
71
Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and 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...
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...
71
Factors Affecting Drug Biotransformation: Physicochemical and Chemical Properties of Drugs
250
A drug's physicochemical properties fundamentally influence its metabolism. For instance, a drug's molecular size and shape critically determine its interaction with enzymes and transporters — larger drugs may face difficulty reaching enzyme active sites, altering their metabolic pathways. The pKa of a drug, which establishes its ionization state, can impact its solubility and absorption, thereby influencing metabolism.
The drug's acidity or basicity is essential in...
The drug's acidity or basicity is essential in...
250


