一个新的基于生理学的直肠吸收的药理动力学模型,使用10种直肠注射药物的临床数据进行评估和验证
Yuri Dancik1, Naresh Mittapelly1, Santosh K Puttrevu1
1Certara UK Limited, Simcyp Division, Level 2-Acero, 1 Concourse Way, Sheffield S1 2BJ, UK.
International journal of pharmaceutics
|July 28, 2023
概括
一个新的基于生理学的药理动力学 (PBPK) 模型准确地预测了直肠服药后的全身药物度. 该工具有助于了解直肠药物吸收,并开发直肠产品的虚拟生物等价性研究.
科学领域:
- 药理动力学 药理动力学
- 药物运输 药物运输 药物运输
- 计算建模 计算建模
背景情况:
- 肠道药物管理是一种替代途径,但其吸收动态尚未完全理解.
- 基于生理学上的药理动力学 (PBPK) 模型提供了一种机械方法来模拟体内的药物行为.
研究的目的:
- 开发和验证PBPK模型,用于预测直肠服药后的全身药物度.
- 评估模型在模拟各种药物的药物吸收和处置方面的表现.
主要方法:
- 使用文献数据对直肠生理学的参数化.
- 整合体外释放 (IVRT) 档案来预测药物质量转移.
- 对10种不同的药物进行29项临床研究的模拟.
主要成果:
- 在10种药物中,PBPK模型对8种药物的Cmax,AUC0-t和AUC0-inf有很好的一致性,平均折叠误差 (AFE) 从0.87到2.22.
- 观察到 AUC 值的过度预测是由于数据的限制和 IVRT 资料的相关性而导致的.
- 该模型成功模拟了大多数测试药物的全身药物度,表明了其实用性.
结论:
- 开发的PBPK模型为机械性直肠药物吸收研究提供了有价值的工具.
- 该模型支持对直肠药物产品的虚拟生物等价性方法的发展.
- 对于具有复杂排泄途径或特定释放特征的药物,可能需要进一步细化.
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