基于生理学的药理动力学模型开发和验证,用于测试佩多酸口服悬浮剂和参考片剂配方的生物等价性
Benny M Amore1, Nikunjkumar Patel2, Priya Batheja1
1Esperion Therapeutics, Inc., Ann Arbor, MI 48108, USA.
Pharmaceutics
|May 27, 2023
概括
贝佩多酸口服悬浮剂与其即时释放片具有生物等价性. 基于生理学的药理动力学模型预测吸收没有显著差异,可能避免临床生物等价性研究.
科学领域:
- 药理动力学和药物输送方法
- 在药理学中的计算建模.
- 生物制药科学 生物制药科学
背景情况:
- 班佩多酸是一种降脂剂.
- 评估不同剂型之间的生物等价性对于监管批准至关重要.
- 基于生理学的药理动力学 (PBPK) 建模为生物等价性评估提供了一个预测方法.
研究的目的:
- 为了评估bempedoic酸口服悬浮剂与其即时释放 (IR) 片剂配方相比的生物等价性.
- 使用基于生理学的药理动力学 (PBPK) 模型来预测生物等价性.
- 为口服 суспензия配方定义生物制药安全空间.
主要方法:
- 开发了一种机械PBPK模型,使用临床质量平衡,体外溶解,可溶性和透性数据.
- 与观察到的临床药理动力学数据对PBPK模型进行了验证.
- 在各种条件下,口服悬浮剂和红外线药片配方之间的模拟生物等价性.
主要成果:
- PBPK模型模拟预测了生物等价性,Cmax和AUC的几何平均比值位于90%的置信区间内.
- 敏感性分析表明,胃过境时间对预测的影响最小.
- 用于口服悬浮剂的生物制药安全空间是由颗粒大小和溶液中药物的分量定义的.
结论:
- PBPK建模预测,bempedoic酸口服悬浮剂与成年人中的IR片具有生物等价性.
- 这两种配方的吸收速度和程度不太可能在临床上有所不同.
- 这些发现表明,对于口服悬浮剂,可能不需要进行临床生物等价性研究.
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