基于生理学的万科米辛药物动力学建模及其与新生儿人口药物动力学模型的比较
Ailing Cao1, Qiaoxi Li2, Minzhen Han3
1Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Journal of clinical pharmacology
|September 3, 2024
概括
基于生理学的药理动力学 (PBPK) 和人口药理动力学 (PopPK) 模型有助于在新生儿中给定万科米辛剂量. PBPK在初始剂量方面表现出色,而PopPK贝叶斯预测在随后的调整方面更好,尽管早期新生儿需要进一步精确的剂量工具.
科学领域:
- 药理动力学 药理动力学
- 新生儿医学 新生儿医学
- 计算建模 计算建模
背景情况:
- 由于治疗窗口狭窄和高可变性,新生儿的万科米辛剂量具有挑战性.
- 基于生理学的药理动力学 (PBPK) 和人口药理动力学 (PopPK) 模型是精确剂量的关键.
研究的目的:
- 为成人和儿科患者群体开发和验证万科米辛PBPK模型.
- 将PBPK模型的预测与新生儿发表的PopPK模型进行比较.
- 评估PBPK和PopPK模型在新生儿中优化万科米辛剂量的实用性.
主要方法:
- 开发了Vancomycin的PBPK模型.
- 验证了PBPK模型与观察到的万科米辛度相比.
- 在230名新生儿 (月经后25-45周) 中,比较了PBPK模型的预测与已发表的PopPK模型 (先验和贝叶斯模型).
主要成果:
- 开发的PBPK模型表现出良好的预测性能.
- 由于生理学描述,PBPK模型在初始万科米辛剂量优化方面具有优势.
- 波普克贝叶斯预测在新生儿随后的万科米辛剂量优化方面表现优异.
结论:
- PBPK和PopPK模型是对新生儿的万科米辛剂量进行补充的工具.
- 对于初始剂量来说,PBPK模型是有利的,而PopPK贝叶斯方法对于持续的调整来说更好.
- 需要进一步的研究,以改善非常早期的早产新生儿 (月经后年龄<36周) 的精确剂量工具.
相关概念视频
Analysis of Population Pharmacokinetic Data
240
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...
240
Pharmacokinetic Models: Comparison and Selection Criterion
50
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.
50
Pharmacokinetic Models: Overview
621
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...
621
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
Mechanistic Models: Overview of Compartment Models
72
Mechanistic models, a category encompassing both physiological and compartmental modeling, differ from empirical models' approaches to incorporating known factors about the systems being modeled. Empirical models describe data with minimal assumptions, while mechanistic models aim to provide a robust description of available data by specifying assumptions and integrating known factors about the system. Compartmental analysis is a key example of a mechanistic model in pharmacokinetics and...
72
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


