一个基于生理学的药理动力学模型,用于预测肝硬化患者的全身度
Faleh Alqahtani1, Abdullah H Alruwaili1, Mohammed S Alasmari1
1Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Pharmaceuticals (Basel, Switzerland)
|December 23, 2023
概括
一个新的基于生理学的药理动力学模型准确地预测了肝硬化患者对丹塞的药物暴露. 该模型有助于调整肝脏疾病的丹塞剂量,以确保患者的安全.
科学领域:
- 药理动力学 药理动力学
- 药物新陈代谢 药物新陈代谢
- 肝脏疾病 肝脏疾病
背景情况:
- 丹塞特朗通常用于癌症和术后患者的恶心和吐.
- 肝功能障碍可能导致丹塞的积累和不良事件.
研究的目的:
- 开发一种基于生理学的药理动力学 (PBPK) 模型,用于ondansetron.
- 预测健康个体和肝硬化患者的丹塞暴露.
主要方法:
- 使用了基于人口的PBPK模拟器PK-Sim.
- 对健康和肝硬化群体进行了模拟.
主要成果:
- 该PBPK模型准确地描述了两组Ondansetron的药理动力学.
- 与轻度肝硬化 (Child-Pugh A) 相比,在严重肝硬化 (Child-Pugh C) 中,丹塞暴露增加了一倍.
- 对于肝硬化患者,剂量调整是必要的.
结论:
- 开发的PBPK模型成功地预测了Ondansetron的药理动力学.
- PBPK模型是调整肝硬化患者的丹塞剂量的宝贵工具.
相关概念视频
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
40
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,...
40
Physiological 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
Pharmacokinetic Models: Overview
706
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...
706
Compartment Models: Two-Compartment Model
5.5K
The two-compartment model divides the body into central and peripheral compartments to account for varying blood perfusion rates among organs and tissues, affecting drug distribution. The central compartment includes blood and highly perfused tissues with rapid drug distribution, while the peripheral compartment contains tissues with slower drug distribution. After a single IV bolus dose, the drug concentration is high in plasma and low in tissues. The drug distribution between compartments...
5.5K
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
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


