使用最小PBPK模型对贝塔梅他松药理学进行跨物种元分析
Congyu Zhang1, William J Jusko1
1Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
Biopharmaceutics & drug disposition
|November 18, 2025
概括
在七种物种中分析了贝他他 (BET) 药理动力学,使用全米缩放和最小生理基础药理动力学 (mPBPK) 模型. 特定物种的吸收和清除率最好解释 BET.
科学领域:
- 药理动力学和药物新陈代谢
- 比较药理学比较药理学
- 基于生理学的药理动力学建模
背景情况:
- 贝塔米他 (BET) 是一种强大的皮质类固醇,具有广泛的治疗应用.
- 了解BET的物种间的药理动力学 (PK) 变异性对于准确的风险评估和剂量推断至关重要.
- 现有的关于不同物种BET PK的数据是分散的,需要统一分析.
研究的目的:
- 在多种物种中描述和比较贝他美沙 (BET) 的药理动力学 (PK) 概况.
- 评估传统的全度量缩放和最低生理学基础的药理动力学 (mPBPK) 模型的实用性,以预测BET PK.
- 为了确定驱动BET倾向物种间差异的关键因素.
主要方法:
- 在七种物种中对BET PK参数进行文献审查和内部数据编制.
- 应用传统的基于体重 (BW) 的全尺度缩放方法.
- 开发和实施一个包含生理参数和物种特异性数据的最小生理基础药理动力学 (mPBPK) 模型.
主要成果:
- BET的明显清除 (CL/F) 显示出与体重 (BW) 具有很强的相关性,使用全米缩放 (R 2 = 0.93).
- 该mPBPK模型成功地捕获了五种物种的BET PK配置文件,并保留了分区系数 (Kp = 0.99).
- 特定物种的清除 (CL) 值和吸收率对于PK数据的最佳合适性至关重要.
结论:
- 贝塔松的分布特性在很大程度上保持在物种之间.
- 特定物种的吸收率和清除值是BET PK变异性的关键决定因素.
- mPBPK模型为了解和预测各种物种的BET配置提供了有价值的框架.
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