在儿科中使用生理学基础的药动力学建模进行克隆丁的最佳剂量推
Venkata Yellepeddi1,2, Sharlo Bayless1,3, Madison Parrot2
1Division of Clinical Pharmacology (VKY, CMS), Department of Pediatrics, University of Utah, UT.
概括
这项研究建议使用生理学基础的药理动力学 (PBPK) 建模,为儿科患者推最佳的克洛尼丁剂量. 这些发现为新生儿戒断综合征 (NAS) 和ADHD治疗提供了基于证据的剂量.
科学领域:
- 药理学 药理学是指药理学的学科.
- 儿科医学 儿科医学
- 计算机建模 计算建模
背景情况:
- 克隆丁在儿科中经常用于治疗新生儿戒断综合征 (NAS),ADHD,镇静和图雷特综合征等疾病.
- 目前对于儿童使用克洛尼丁的剂量指南缺乏共识,导致治疗的变化.
- 基于生理学上的药理动力学 (PBPK) 建模为确定最佳儿科剂量提供了一个有前途的方法.
研究的目的:
- 为儿童群体建立基于证据的克洛尼丁剂量建议.
- 利用PBPK建模来模拟和预测儿童中克隆尼丁的药理动力学.
- 为了确定最佳的克洛尼丁剂量,以达到最大的α-2上腺活性的目标治疗度.
主要方法:
- 一个儿科PBPK模型是通过扩展现有的成年模型,使用净化过程的本体生成方程来开发的.
- 模型验证涉及将模拟数据与临床药理动力学数据进行比较,通过视觉预测检查和绝对折叠误差 (AFE) 进行评估.
- 在一个虚拟的儿科群体中进行了模拟,以根据目标EC50度对α-2中央激动剂活性来确定最佳剂量.
主要成果:
- 成人和儿科PBPK模型都表现出良好的预测性能,超过90%的观察数据在95%的预测间隔内.
- 绝对折叠误差 (AFE) 值为预测与观察到的克隆尼丁血度的2倍之内.
- 最佳口服剂量建议被确定为新生儿30μg/kg/天,6-17岁儿童0.9 mg/天.
结论:
- 开发的儿科PBPK模型,从成人模型缩放,成功为各种儿科年龄组提供了最佳的克洛尼丁剂量建议.
- 这种PBPK建模方法可以进一步扩展,以探索不同的施用途径和额外的儿科年龄范围.
- 这项研究有助于在儿科护理中建立标准化和有效的克洛尼丁剂量策略.
相关概念视频
01:26Pharmacokinetic 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
01:13Physiological Pharmacokinetic Models: Assumption with Protein Binding
31
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...
31
01:06Model 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
01:21Factors Affecting Drug Response: Overview
1.9K
When it comes to infants and young children, they are typically administered smaller doses of medication in comparison to adults. This is primarily because their organ functions still need to fully develop, meaning their bodies are not as efficient at metabolizing or eliminating drugs. Additionally, their blood-brain barrier is more permeable than in adults. As a result, high concentrations of drugs can easily penetrate the central nervous system (CNS), potentially leading to neurological...
1.9K
01:20Pharmacokinetic Models: Overview
582
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...
582
01:23Nonlinear Pharmacokinetics: Dependence of Elimination Half-Life and Dose Clearance
81
The elimination half-life and drug clearance of drugs following nonlinear kinetics can vary with dosage. The Michaelis-Menten parameters and drug concentration influence these factors. As the dose increases, the elimination half-life tends to lengthen, resulting in a reduction in clearance and a disproportionately larger area under the curve. The total clearance can be derived from the Michaelis-Menten equation for drugs following a one-compartment model.
A study on guinea pigs examined the...
A study on guinea pigs examined the...
81