在各种物种中使用最小的基于生理学的药理动力学模型对levamisole吸收和处置的元分析
ChunFu Cheng1, Yoo-Seong Jeong1, William J Jusko1,2
1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY USA.
Journal of pharmaceutical investigation
|January 8, 2026
概括
莱瓦米索尔在18种物种中表现出一致的药动力学特性,口服生物利用率在50-80%之间. 最小生理学基础的药理动力学 (mPBPK) 建模有效地比较了levamisole药理动力学的物种间差异.
科学领域:
- 药理学 药理学是指药理学的学科.
- 兽医医学 兽医医学 兽医医学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 列瓦米索尔是一种重要的免疫刺激剂和抗寄生虫剂.
- 了解其跨物种的药理动力学 (PK) 概况对于有效的治疗用途至关重要.
研究的目的:
- 在口服 (PO) 和静脉注射 (IV) 后,评估和比较18种物种中levamisole的药理学数据.
- 评估全米缩放和最小生理学基础的药理动力学 (mPBPK) 建模用于跨物种PK比较的适用性.
主要方法:
- 收集和分析了18个物种的PK数据,重点关注8个物种,这些物种有足够的数据用于联合建模.
- 采用传统的全度量缩放来检查清除率 (CL),分布量 (Vss),吸收速率常数 (ka) 和与体重 (BW) 相对应的生物可用性 (F).
- 使用了通用最小生理学基础的药理动力学 (mPBPK) 模型来描述PK配置文件并确定特定物种的参数.
主要成果:
- 所有度缩放显示Vss的相关性很好 (b=0.89),但CL,ka和F的相关性较弱,CL的异常值是子.
- 一个两部分模型 (2CM) 充分捕获了二次指数 PK 配置文件.
- 该mPBPK模型包含了特定物种的组织分区系数 (Kp),准确地描述了观察到的PK配置文件,特别是在猪和.
- 在大多数物种中,口服生物利用率 (F) 始终很高 (50-80%),但山羊除外.
结论:
- 莱瓦米索尔表现出快速吸收,广泛的新陈代谢,以及在各种物种中基本一致的PK特性.
- 最小的PBPK建模提供了一个有价值的框架,用于比较levamisole药理动学的跨物种决定因素.
- 这些发现支持使用mPBPK来预测不同动物模型中的药物行为.
相关概念视频
01:07Physiological Pharmacokinetic Models: Incorporating Hepatic Transporter-Mediated Clearance
269
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,...
269
01:26Pharmacokinetic Models: Comparison and Selection Criterion
328
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.
328
01:20Pharmacokinetic Models: Overview
1.8K
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...
1.8K
01:20Measurement of Bioavailability: Pharmacodynamic Methods
228
Pharmacodynamic methods provide insights into a drug's effects on physiological processes over time and play a crucial role in understanding bioavailability and therapeutic efficacy. These methods can be broadly classified into acute pharmacological and therapeutic response approaches, each with distinct mechanisms and applications.The acute pharmacological response method directly correlates a drug's physiological effects, such as ECG or pupil diameter changes, to its time course in the body.
228
01:14Model Approaches for Pharmacokinetic Data: Compartment Models
519
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...
519
01:30Measurement of Bioavailability: Pharmacokinetic Methods
254
Pharmacokinetics is a vital branch of pharmacology that examines how drugs are absorbed, distributed, metabolized, and excreted by the body. Two key methodologies in pharmacokinetics are plasma drug concentration studies and urinary drug excretion analyses, both of which provide critical insights into a drug's therapeutic efficacy and bioavailability.Plasma Drug Concentration-Time StudiesPlasma drug concentration-time studies involve analyzing blood samples at specific intervals to quantify...
254