食品成分对异化的PK的影响用生理学基础生物制药建模量化解释使用生理学基础生物制药建模
Xavier J H Pepin1, Sandra Suarez-Sharp2
1Regulatory Affairs, Simulations Plus, Inc., Lancaster, California, USA. Xavier.pepin@simulations-plus.com.
The AAPS journal
|April 24, 2024
概括
这项研究开发了一种基于生理学的生物制药模型 (PBBM),以预测食物如何影响异化 (INH) 药理动力学 (PK). 该模型准确地解释了富含碳水化合物的食如何降低INH吸收和有效性.
科学领域:
- 药物动力学和生物制药学
- 计算机建模 计算建模
- 药物新陈代谢 药物新陈代谢
背景情况:
- 伊索尼亚 (INH) 药理动力学 (PK) 受到食物摄入的显著影响,影响治疗疗效.
- 了解这些相互作用对于优化结核病治疗至关重要.
- 现有的模型往往缺乏有关食物影响的机械细节.
研究的目的:
- 开发和验证一种以生理学为基础的生物制药模型 (PBBM) 对异化 (INH).
- 通过机制阐明不同类型的食品对INH和乙-异化 (Ac-INH) 药理学的影响.
- 为了将N-乙转移酶2 (NAT2) 机体生成和光线药物降解纳入模型.
主要方法:
- 使用已公布的INH PK数据和药物特性建立并验证了一种 PBBM.
- 开发了一个专门的NAT2本体生成模型,结合了迈凯利斯·门的参数.
- 提出了一种基于食成分 (减糖) 的光线药物降解的新式方程式.
- 纳入了针对胆汁盐度和胃空化的特定食品调整.
主要成果:
- PBBM准确地预测了富含碳水化合物的饮食对INH药理动学的负面影响.
- 该模型成功地解释了不同乙化剂表型的系统前和系统代谢.
- 确定了光线药物降解和食物诱导的生理变化是关键因素.
结论:
- 基于生理学的生物制药建模为预测食物对INH PK的影响提供了强大的框架.
- 饮食成分,特别是碳水化合物和降解糖,显著改变INH的生物可用性.
- 开发的模型为个性化剂量策略和药物开发提供了有价值的工具.
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