美国食品和药物管理局 (FDA) 和欧洲药物管理局 (EMA) 对有限吸收时间 (F.A.T.) 的应用进行破坏性科学监督. 口服药物吸收的概念:科学和监管变化的时间
Elias Toulitsis1, Athanasios A Tsekouras2,3, Panos Macheras1,3
1Faculty of Pharmacy, National and Kapodistrian University of Athens, 15784 Athens, Greece.
Pharmaceutics
|November 27, 2024
概括
基于生理学的有限时间药理动力学模型提供了比传统方法更准确的口服药物吸收描述. 这项研究证明了它们在分析药物吸收特征方面的有用性,并支持改善药理动力学分析的监管变化.
科学领域:
- 药理动力学 药理动力学
- 药物吸收建模 药物吸收建模
- 计算生物学 计算生物学
背景情况:
- 药理动力学中无限吸收时间的传统概念在生理学上是不合理的.
- 有限吸收时间 (F.A.T.) 和基于生理学的有限时间药理动力学 (PBFTPK) 模型提供了更准确的口服药物吸收的描述.
- 以前的分析强调了吸收速率常数在描述胃肠道药物吸收时的局限性.
研究的目的:
- 使用PBFTPK模型重新分析口服药物吸收数据.
- 开发方程来估计从口服数据中吸收剂量的分数和生物可用分数,用于单间模型药物.
- 为分析口服药物吸收特征提供一个生理上健全的框架.
主要方法:
- 使用PBFTPK模型重新分析了七个数据集 (托,阿姆洛迪平,西奥菲林,莱沃诺格斯特勒).
- 从口服吸收数据来估计关键药理动力学参数的方程的开发.
- 应用PBFTPK模型来确定吸收阶段,持续时间,输入速率和总吸收时间.
主要成果:
- 对于所有分析的药物来说,对吸收阶段的数量 (1-3),每个阶段的持续时间,药物输入率和总吸收时间进行了有意义的估计.
- 总吸收持续时间从0.75小时 (基托) 到11.6小时 (Theodur).
- 估计了基托和两个神叶素配方的生物可用分数.
结论:
- PBFTPK模型提供了对口服药物吸收特征的详细见解.
- 这些模型提供了一个计算框架,以取代在药理动力学分析中生理上不健全的"吸收速率常数"概念.
- 这项研究支持了对药理动力学分析和生理基础药理动力学 (PBPK) 研究的科学和监管变革的需要.
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