在接受阿纳金拉的重症儿童中,基于生理学上的药理动力学建模在体外生命支持时接受了阿纳金拉
Samuel Dubinsky1, Abdullah Hamadeh1, Carina Imburgia2
1School of Pharmacy, Faculty of Science, University of Waterloo, Waterloo, ON, Canada.
Clinical pharmacokinetics
|September 27, 2024
概括
开发了一种新的生理学基础的药理动力学 (PBPK) 模型,用于在体外生命支持 (ECLS) 上的重症儿童的阿纳金拉. 这个模型准确地预测了药物度,并建议与健康儿童相比,类似的anakinra暴露.
科学领域:
- 药理动力学 药理动力学
- 儿科重症监护中心儿童重症监护中心
- 药物指标 (Pharmacometrics) 是一个指标.
背景情况:
- 危急疾病和体外生命支持 (ECLS) 改变了药物的药理动力学.
- 精确的药物剂量在ECLS的重症儿童中具有挑战性.
研究的目的:
- 在ECLS的儿科患者中开发一个基于生理学的药理动力学 (PBPK) 模型用于anakinra.
- 在这个复杂的患者群体中指导anakinra药疗.
主要方法:
- 从健康人群中推断出一个PBPK模型,从健康人群中推断到重症儿童中.
- 将持续置换疗法 (CRRT) 和体外膜氧化 (ECMO) 分区纳入PBPK模型.
- 使用观察到的患者数据验证了模型,并进行了in-silico剂量模拟.
主要成果:
- 开发的ECLS-PBPK模型准确地预测了ECLS青少年的阿纳金拉血度.
- 在体模拟表明,在ECLS的青少年和健康人群中,阿纳金拉暴露率相似.
结论:
- 这是第一个anakinra ECLS-PBPK模型,可以预测同时接受CRRT和ECMO的患者的药物度.
- 模型和模拟数据可以为anakinra的剂量提供信息,并帮助将来在重症儿童中设计临床试验.
更多相关视频
相关概念视频
Pharmacokinetic Models: Comparison and Selection Criterion
48
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.
48
Pharmacokinetic Models: Overview
607
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...
607
Model Approaches for Pharmacokinetic Data: Physiological Models
36
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...
36
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
63
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...
63
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
34
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,...
34
Physiological Pharmacokinetic Models: Assumption with Protein Binding
36
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...
36


