基于生理学的药理动力学 (PBPK) 模型的近期进展:基于文献识别的审查
He Huang1, Wenjing Zhao1, Ning Qin1
1School of Energy and Environmental Engineering, University of Science and Technology Beijing, Beijing 100083, China.
Toxics
|June 26, 2024
概括
基于生理学的药理动力学/毒理动力学 (PBPK) 模型对于理解化学影响至关重要. 本次审查强调了它们在医学中的广泛使用和在环境科学中不断增长的风险评估应用.
科学领域:
- 环境科学 环境科学
- 毒理学 毒理学 毒理学
- 药理动力学 药理动力学
背景情况:
- 以生理学为基础的药理动力学/毒理动力学 (PBPK/PBTK) 模型模拟使用生物特性的化学反应.
- PBPK 模型在医学,环境科学和生态学方面取得了成功,经历了一个世纪的发展.
- 缺乏对PBPK模型进展的系统审查,特别是在水生环境研究中.
研究的目的:
- 系统地审查PBPK模型的进展情况和主要研究方向.
- 全面了解PBPK模型在水生环境研究中的应用.
- 分析趋势并确定未来的研究差距和解决方案.
主要方法:
- 从1996年到2024年3月收集了PBPK模型的3974篇文章.
- 利用CiteSpace进行关键字共发生和集群映射来对研究领域进行分类.
- 进行了图书统计分析,以确定趋势和增长模式.
主要成果:
- 医学研究主导了PBPK应用,其中"药物评估" (55%) 是最大的领域,以及"跨物种预测"",药物相互作用"和"儿科和怀孕药物开发".
- 环境研究应用的显著增长,重点是预测化学残留物和将内部与外部暴露联系起来.
- 尽管存在特定物种的参数限制,但PBPK模型对于理解化学生物相互作用是有效的.
结论:
- PBPK模型对于理解生物体中的化学机制至关重要.
- 环境应用正在迅速扩大,为生态和人类健康风险提供了洞察力.
- 将PBPK与QSAR,贝叶斯方法和机器学习集成,可以解决当前研究的局限性.
相关概念视频
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
38
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,...
38
Model Approaches for Pharmacokinetic Data: Physiological Models
41
Physiological models in pharmacokinetics are instrumental in understanding the distribution and elimination of drugs within the body. These models describe the drug concentration within target organs, influenced by factors such as drug uptake, tissue volume, and blood flow. Drug uptake is governed by the partition coefficient, which signifies the drug concentration ratio in tissue to that in the blood. The blood flow rate to a specific tissue is expressed as Qt, and the rate of change in tissue...
41
Pharmacokinetic Models: Overview
647
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.
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
647
Pharmacokinetic Models: Comparison and Selection Criterion
66
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.
66
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
68
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...
68
Analysis of Population Pharmacokinetic Data
252
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...
252


