评估用于预测药物分布到母乳中的数学模型 - - 考虑到生物异质性
Sumin Heo1,2, Andrew S Butler1, Marina Stamouli Simoncioni1
1Medicines and Healthcare products Regulatory Agency (MHRA), London, United Kingdom.
Frontiers in pharmacology
|December 16, 2024
概括
母乳的成分差异很大,影响药物传递给婴儿. 当前的模型往往错误地预测药物水平,需要改进的计算方法来解释母乳.
科学领域:
- 药理动力学 药理动力学
- 药物代谢和运输 药物代谢和运输
- 新生儿和母亲的健康.
背景情况:
- 许多母亲在母乳养期间使用药物,但婴儿安全知识有限.
- 母乳的成分 (脂肪,蛋白质,pH) 是高度可变的,影响药物积累.
- 预测婴儿药物暴露的现有数学模型往往缺乏对各种母乳数据的验证.
研究的目的:
- 评估现有数学模型的可靠性,以预测母乳中药物分布.
- 研究用于预测药物转移的替代方法,考虑到母乳的生理异质性.
- 改进在乳房养期间评估婴儿药物暴露的in silico方法.
主要方法:
- 收集的牛奶与血 (M/P) 比率和药物的物理化学性质.
- 通过改变牛奶pH值和奶油度来评估模型可靠性.
- 研究了脂质和蛋白质结合以及电离效应的替代预测方法.
主要成果:
- 现有的模型错误预测了超过40%的药物.
- 模型对牛奶pH值有很高的敏感性或对奶油的敏感性有限.
- 替代方法在预测脂质分布方面提供了适度的改进,但蛋白质结合和电离的影响很小.
结论:
- 考虑到母乳的生物异质性对于准确的药物分配模型至关重要.
- 需要进一步了解生理分布机制,以完善in silico工具.
- 改进的模型对于在母乳养期间支持婴儿和母亲健康至关重要.
相关概念视频
Pharmacokinetic Models: Comparison and Selection Criterion
38
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.
38
Model Approaches for Pharmacokinetic Data: Distributed Parameter Models
56
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...
56
Pharmacokinetic Models: Overview
578
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...
578
Multicompartment Models: Overview
93
Multicompartment models are mathematical constructs that depict how drugs are distributed and eliminated within the body. They segment the body into several compartments, symbolizing various physiological or anatomical areas connected through drug transfer processes such as absorption, metabolism, distribution, and elimination.
These models offer a more comprehensive representation of drug behavior in the body than one-compartment models. They accommodate the complexity of drug distribution,...
These models offer a more comprehensive representation of drug behavior in the body than one-compartment models. They accommodate the complexity of drug distribution,...
93
Mechanistic Models: Compartment Models in Individual and Population Analysis
27
Mechanistic models are utilized in individual analysis using single-source data, but imperfections arise due to data collection errors, preventing perfect prediction of observed data. The mathematical equation involves known values (Xi), observed concentrations (Ci), measurement errors (εi), model parameters (ϕj), and the related function (ƒi) for i number of values. Different least-squares metrics quantify differences between predicted and observed values. The ordinary least...
27
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
26
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,...
26


