用一块石头杀死几只鸟:一个多指标种群的药理动力学模型和贝叶斯估计器,用于肠道涂层的甲
Yeleen Fromage1, Hamza Sayadi1, Kevin Koloskoff2,3
1Department of Pharmacology, Toxicology and Pharmacovigilance, CHU de Limoges, Limoges, France.
这项研究使用有限的抽样策略开发了基酸 (MPA) 的人口药理动力学模型. 该模型准确地估计了移植和自身免疫疾病患者个性化剂量的MPA AUC.
科学领域:
- 药理动力学 药理动力学
- 药物的新陈代谢和处置
- 临床药理学 临床药理学
背景情况:
- 基酸 (MPA) 的药理动力学是高度可变的.
- 目前对MPA的种群药理动力学 (popPK) 模型是有限的,特别是在特定患者种群中估计AUC.
- 肠涂层甲 (EC-MPS) 是广泛使用的,但由于MPA水平的变化,需要精确的剂量.
研究的目的:
- 为MPA开发一个popPK模型.
- 使用有限采样策略 (LSS) 为MPA AUC创建贝叶斯估计 (MAP-BE) 方法.
- 在固体器官移植 (SOT),造血干细胞 (HSC) 和自身免疫性疾病 (AID) 患者中验证模型和LSS.
主要方法:
- 提取了PK配置文件,并将其分为开发和验证套件.
- 使用SAEM算法选择了一个带有双马吸收的单间模型.
- 使用MAP-BE和LSS预测MPA AUC,并与参考值进行比较.
主要成果:
- 一个带有双马吸收和第一阶排泄的单间模型最好地描述了MPA PK.
- 最优的LSS包括剂后20分钟,2小时和4小时的样本.
- 在低预测误差 (rMPE -2.67%至 -4.91%) 和RMSE (13.55%至13.47%) 的验证集中,LSS表现良好.
结论:
- 开发的双马吸收模型与MPA PK数据准确匹配.
- 带有LSS的MAP-BE提供了一个可靠的工具来个性化EC-MPS (MPA) 剂量.
- 这种方法支持在SOT,HSC和AID患者中优化MPA剂量.
更多相关视频
08:59An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
11:34A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
相关概念视频
Analysis of Population Pharmacokinetic Data
Pharmacokinetic Models: Overview
There are three primary types of models: empirical, compartment, and physiological. Empirical models, with minimal...
Model Approaches for Pharmacokinetic Data: 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...
One-Compartment Open Model for IV Bolus Administration: General Considerations
The drug's presence in the body is defined by an equation representing the difference between the rates of drug entry and exit. Key parameters—elimination rate constant,...
Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
A recent model describes pravastatin's hepatobiliary excretion,...
Pharmacokinetic Models: Comparison and Selection Criterion
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.
