对于患有血管异常的儿童,阿尔佩利西布的固定剂量:我们能做得更好吗?
Amandine Remy1,2, Albert Etingin3, Paul Gavra4
1General Pediatric Fellowship Program, Sainte-Justine University Hospital, Université de Montréal, Montreal, Canada.
British journal of clinical pharmacology
|January 24, 2025
概括
对儿童严重血管形的阿尔佩利西布剂量显示出很高的可变性. 药物动力学数据对于安全有效的治疗至关重要,因为目前的固定的剂量与体重无关.
科学领域:
- 药理学 药理学是指药理学的学科.
- 遗传学 遗传学 是一个
- 儿科 儿科 儿科
背景情况:
- 严重的血管形 (VM) 显著损害生活质量,并可能导致器官功能障碍.
- 在VM中,PI3K/AKT/mTOR通路中的体质激活突变很常见.
- 阿尔佩利西布是一种PIK3CA抑制剂,已被FDA批准用于儿童的PIK3CA相关过度生长综合征 (PROS).
研究的目的:
- 报告严重VM的儿科患者的新型alpelisib药理动力学 (PK) 数据.
- 提供数据支持在儿童中做出明智的阿尔佩利西布剂量决定.
- 为了解决目前体重独立的固定剂量缺乏PK数据的问题.
主要方法:
- 包括9名患有严重VM的儿科患者 (4名PROS,5名其他VM).
- 阿尔佩利西布的固定剂量为50毫克/天.
- 曲线下的面积 (AUC) 被测量以评估药物暴露.
主要成果:
- 在儿科患者中,阿尔佩利西布AUC表现出很高的变化 (CV = 58%).
- 平均年龄为10.5岁,平均体重为43公斤.
- AUC显示与患者体重的相关性.
结论:
- 固定50毫克/天的阿尔佩利西布剂量导致儿童的药物暴露高度变化.
- 由于未知的短期和长期不良影响,迫切需要基于体重的剂量.
- 进一步的PK研究对于优化儿科VM中的alpelisib治疗至关重要.
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