慢性病和基于生理学的药理动力学建模:对现有模型的批判性审查
Ammara Zamir1, Faleh Alqahtani2, Muhammad Fawad Rasool1
1Department of Pharmacy Practice, Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
Expert opinion on drug metabolism & toxicology
|January 25, 2024
概括
基于生理学的药理动力学 (PBPK) 模型有助于在慢性病 (CKD) 中评估药物暴露. 本综述综合了CKD的PBPK模型,证实了它们在管理药物治疗和预防不良影响方面的准确性.
科学领域:
- 药理动力学 药理动力学
- 药理动力学是什么 药理动力学
- 系统生物学 系统生物学
背景情况:
- 基于生理学的药理动力学 (PBPK) 建模对于药物暴露评估至关重要,特别是在慢性病 (CKD) 等患者群体中,临床试验具有挑战性.
- 了解CKD中的药物行为对于优化治疗结果和最大限度地减少不良事件至关重要.
研究的目的:
- 审查并对已发表的PBPK模型进行对比,这些模型是专门针对慢性病 (CKD) 开发的.
- 分析药物和系统特定输入参数以及CKD中PBPK模型的模型评估标准.
- 为研究人员提供关于应用PBPK模型来管理CKD患者药物治疗的见解.
主要方法:
- 在四个数据库中进行系统的文献搜索 (6月13日至2023年7月10日).
- 纳入/排除标准用于确定CKD中PBPK模型的相关研究.
- 提取和阐述药物物理化学参数,CKD的生理变化 (例如,GFR,蛋白结合,CYP酶) 和模型评估指标.
主要成果:
- 为CKD中各种药物编制了PBPK模型的综合数据集.
- 详细介绍了与CKD中药物处置相关的生理参数的关键变化.
- 模型评估表明,大多数用于CKD药物的PBPK模型都处于可接受的两倍误差范围内,证明了预测准确性.
结论:
- PBPK建模是预测药物暴露和指导CKD患者治疗的宝贵工具.
- 审查的PBPK模型证明了药物治疗管理的可靠性,旨在提高疗效和减少副作用.
- 本综述是研究人员和临床医生在CKD药物治疗中使用PBPK建模的资源.
相关概念视频
01:26Pharmacokinetic Models: Comparison and Selection Criterion
73
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.
73
01:20Pharmacokinetic Models: Overview
694
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...
694
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
39
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,...
39
01:06Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
69
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...
69
01:15Model Approaches for Pharmacokinetic Data: Physiological Models
46
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...
46
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
45
Physiological models with protein binding in pharmacokinetics offer a sophisticated approach to understanding drug disposition. These models consider drug-protein interactions, enabling them to effectively predict drug concentrations in different organs and tissues. This precision aids in accurate drug dosing, providing a significant advantage over conventional models. A key process within these models is equilibration, which ensures that drug concentrations achieve a steady state within the...
45