不同脂肪度的食物对阿莱克提尼布暴露的影响:一个随机交叉药理动力学试验
Daan A C Lanser1, Simon P de Leeuw1,2, Esther Oomen-de Hoop1
1Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, the Netherlands.
概括
与低脂肪酸奶一起服用alectinib可显著降低对非小细胞肺癌的阿纳普拉斯性淋巴瘤激酶阳性患者的药物暴露. 自选的午餐是优化alectinib生物可用性的安全替代方案.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 临床医学 临床医学
背景情况:
- 阿莱克提尼布是治疗晚期性淋巴瘤激酶阳性 (ALK+) 非小细胞肺癌 (NSCLC) 的关键治疗方法.
- 已经确定了alectinib (435 ng/mL) 的治疗暴露值,但许多患者无法达到它.
- 阿列克提尼布的口服吸收受到食物摄入的影响,因此需要进一步研究食品药物相互作用,以提高生物可用性.
研究的目的:
- 为了研究不同食对ALK+ NSCLC患者alectinib暴露的影响.
- 确定优化alectinib生物可用性和治疗功效的饮食建议.
主要方法:
- 在ALK+ NSCLC患者中进行了一项随机的3期交叉研究.
- 阿莱克提尼布剂量与大陆式早餐,低脂肪酸奶或自选的午餐一起服用.
- 测量了alectinib的最低度 (Ctrough),以评估药物暴露.
主要成果:
- 与大陆式早餐或自行选择的午餐相比,当与低脂肪酸奶一起服用时,alectinib的暴露明显较低 (14-20%).
- 与自己选择的午餐一起服用alectinib与大陆早餐相比,没有改变暴露.
- 较高的患者比例 (35%) 在食用低脂肪酸奶时未能达到alectinib值.
结论:
- 在alectinib和低脂肪酸奶之间存在显著的食品药物相互作用,导致药物暴露减少.
- 医生和患者应谨慎避免将alectinib与低脂肪酸奶一起食用.
- 自行选择的午餐代表了对alectinib的安全和患者友好的替代方案.
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