基于模型的药物开发 (MIDD) 方法,以支持IBERDOMIDE的生物制药开发
Caroline Sychterz1, Ping Chen1,2, Ajay Saxena1
1Bristol Myers Squibb, Princeton, New Jersey, USA.
The AAPS journal
|April 29, 2025
概括
伊伯多米德是一种新型多发性骨髓瘤治疗方法,在所有配方中都没有显示食物效应. 建模和模拟证实了持续的全身暴露,无论食物摄入量或配方变化.
科学领域:
- 药理动力学和药物开发
- 瘤学 治疗学 治疗学
- 配方科学科学 配方科学
背景情况:
- 伊伯多米德是BCS III CELMoDTM治疗多发性骨髓瘤的一种药物.
- 在临床开发期间使用了五种配方.
- 以前的研究表明,早期配方对食物没有影响.
研究的目的:
- 为了证明所有 iberdomide 配方,包括预期的商业形式 (ICF) 缺乏食物效应.
- 通过建模和模拟来弥合临床数据上的差距.
- 为了支持ICF的监管提交.
主要方法:
- 使用人口药理动力学 (PK) 模型来评估配方影响.
- 采用基于生理学的药理动力学 (PBPK) 建模,由体外溶解数据提供信息.
- 对关键的药理动力学参数进行了敏感性分析.
主要成果:
- 人口PK建模证实配方不是 iberdomide PK 的共变量.
- 结合体外溶解的PBPK建模,在所有五种配方中都没有显示出食物效应.
- 敏感性分析确定药物释放和透性是关键因素,与BCS III分类保持一致.
结论:
- 总的来说,所有证据都不支持预期的商业化伊伯多米德配方 (ICF) 对食物没有预期的影响.
- 建模和模拟有效地弥合了临床数据上的差距.
- 伊伯多米德的吸收主要由药物释放控制,这与其BCS III特性相一致.
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