阿皮克萨班的生理基础生物制药模型用于生物制药风险评估
Paulo Paixão1, Zvonimir Petric1, José A G Morais1
1Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisbon, 1649-004 Lisboa, Portugal.
Pharmaceutics
|March 27, 2025
概括
基于生理学的生物制药模型 (PBBM) 准确地预测了阿皮克萨班的生物可用性和生物等价性. 120微米以下的较小颗粒大小确保生物等价性,并支持药物开发的生物豁免标准.
科学领域:
- 药物动力学和生物制药学
- 计算机化药物开发 计算机化药物开发
- 配方科学科学 配方科学
背景情况:
- 阿皮克萨班是一种边界BCSIII/IV类药物,在预测生物可用性 (BA) 和生物等价性 (BE) 方面存在挑战.
- 了解配方对阿皮克萨班体内性能的影响对于药物开发至关重要.
- 基于生理学的生物制药模型 (PBBM) 为复杂药物提供了预测框架.
研究的目的:
- 开发和验证PBBM框架,用于预测阿皮克萨班BA和BE.
- 为了研究配方因子 (颗粒大小,颗粒化) 对阿皮克萨班吸收的影响.
- 确定配方特征,确保生物等价性并支持监管决策.
主要方法:
- 将物理化学,配方和药物参数集成到PBBM框架中.
- 利用诺伊斯-惠特尼方程来建模受粒子大小和颗粒度影响的溶解.
- 采用中出策略,将in silico,in vitro和in vivo数据结合起来进行模拟.
主要成果:
- 通过对不同剂量和配方的阿皮克萨班观察到的药理学特征进行验证的 PBBM 预测.
- 在各种条件下证明了BA和BE的可接受的预测准确性.
- 确定了一个"溶解安全空间",为可接受的配方属性提供了洞察力.
结论:
- PBBM有效地预测阿皮克萨班BA和BE,简化药物开发和减少临床试验.
- 颗粒大小<120μm确保与参考配方具有生物等价性.
- 与较小颗粒大小相关的更快的溶解速率与BCS生物豁免标准保持一致,优化药品质量.
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