探索肝功能障碍对pralsetinib药理动学的影响
Kit Wun Kathy Cheung1, Yang Tang2, Doreen Anders3
1Clinical Pharmacology, Genentech, Inc., South San Francisco, CA 94080, USA.
Pharmaceutics
|April 27, 2024
概括
在中度至重度肝功能障碍患者中评估了pralsetinib的药理动力学. 该研究没有发现对药物暴露的显著影响,这表明这些患者不需要调整剂量.
科学领域:
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
- 临床药理学 临床药理学
背景情况:
- 普拉塞替尼是转移性RET融合阳性非小细胞肺癌的激酶抑制剂.
- 肝功能障碍 (HI) 可能会改变pralsetinib的药理动力学 (PK) 由于其初级肝排泄.
- 轻度HI对普拉塞提尼布PK的影响很小.
研究的目的:
- 评估pralsetinib PK,安全性和耐受性在中度和严重HI的受试者中.
- 为了比较患有HI的人与正常肝功能的人中的pralsetinib暴露.
主要方法:
- 在中度和重度HI的受试者中评估了pralsetinib的药理学,安全性和耐受性.
- 肝功能障碍被使用Child-Pugh和国家癌症研究所器官功能障碍工作组 (NCI-ODWG) 标准进行分类.
- 系统性暴露 (AUC0-∞) 在肝功能受损和正常的肝功能组之间进行了比较.
主要成果:
- 中度和严重的HI没有显著改变pralsetinib的全身暴露 (AUC0-∞).
- 对AUC0-∞的几何平均比率 (GMR) 在不同HI分类和正常肝功能中是可比的.
- 与正常肝功能相比,中度和重度HI的AUC0-∞GMR从0.858到1.22不等.
结论:
- 中度和重度肝功能障碍不会有意义地影响pralsetinib的暴露.
- 在中度或重度肝功能障碍患者中,不需要调整pralsetinib的剂量.
- 在患有肝功能障碍的患者中,pralsetinib可以安全地在没有剂量修改的情况下使用.
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