集群高斯-牛顿方法用于快速近似的概率概率:适用于基于生理学的药物动力学模型
Yasunori Aoki1,2, Yuichi Sugiyama2,3
1Drug Metabolism and Pharmacokinetics, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
CPT: pharmacometrics & systems pharmacology
|October 19, 2023
概括
这项研究引入了一种更快的方式来评估在生理学基础药理动力学 (PBPK) 模型中的参数识别能力. 这种新方法使用现有的计算来近似概率概率,为PBPK模型分析节省时间和资源.
科学领域:
- 药理动力学和生理学建模
- 计算生物学 计算生物学
- 统计建模 统计建模
背景情况:
- 基于生理学的药理动力学 (PBPK) 模型对于药物开发至关重要,但由于有限的可观测数据,通常会遭受参数不确定性.
- 传统的参数识别和置信区间估计方法,如概率概率,由于重复的优化,需要大量的计算资源.
- 集群高斯 - 牛顿方法 (CGNM) 提供了高效的参数空间探索,但尚未直接用于概率概括.
研究的目的:
- 开发一种高效的方法来近似PBPK模型中的概率概率.
- 为了减少与参数识别分析相关的计算负担.
- 为了快速估计参数置信区间,并识别参数组合.
主要方法:
- 提出了一种新的方法,通过重复使用来自集群高斯-牛顿方法 (CGNM) 的中间计算结果来估计概率概率.
- 实施了一种技术,可以在没有额外的模型评估的情况下推导出配置概率的上限.
- 扩展了用于快速生成一维和二维概率的方法.
主要成果:
- 在PBPK模型中成功近似了所有未知参数的概率概率,计算时间大大缩短.
- 证明能够在几秒钟内生成参数组合的二维概率概率.
- 在三个不同的PBPK模型中验证了该方法的有效性,显示了其实际适用性.
结论:
- 拟议的方法为PBPK建模中的概率概率近似提供了一个计算效率高的替代方案.
- 这种方法加快了对参数识别性和置信区间的评估,促进了更强大的PBPK模型开发.
- 该技术有望提高PBPK模型分析和应用的速度和效率.
相关概念视频
01:06Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
74
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...
74
01:15Model Approaches for Pharmacokinetic Data: Physiological Models
52
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...
52
01:26Pharmacokinetic Models: Comparison and Selection Criterion
79
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.
79
00:59Model-Independent Approaches for Pharmacokinetic Data: Noncompartmental Analysis
70
Noncompartmental analyses offer an alternative method for describing drug pharmacokinetics without relying on a specific compartmental model. In this approach, the drug's pharmacokinetics are assumed to be linear, with the terminal phase log-linear. This assumption allows for simplified analysis and interpretation of the drug's behavior in the body.
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
One important characteristic of noncompartmental analyses is that drug exposure increases proportionally with increasing doses. This...
70
01:12Analysis of Population Pharmacokinetic Data
267
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...
267
01:14Model Approaches for Pharmacokinetic Data: Compartment Models
107
Compartmental analysis is a widely adopted approach to characterizing drug pharmacokinetics. It uses compartment models that conceptualize the body as a collection of reversibly communicating compartments, each representing a group of tissues exhibiting similar drug distribution characteristics. The movement rate of the drug between these compartments is typically described by first-order kinetics.
Two primary types of compartment models are recognized: mammillary and catenary. The more...
Two primary types of compartment models are recognized: mammillary and catenary. The more...
107