特里夫里丁,甲福明和西米蒂丁之间的OCT2/MATE1相互作用:一个交叉的药理动力学研究
Niels A D Guchelaar1, Stefan A J Buck2, Leni van Doorn2
1Department of Medical Oncology, Erasmus MC Cancer Institute, Dr. Molewaterplein 40, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. n.guchelaar@erasmusmc.nl.
Clinical pharmacokinetics
|July 1, 2024
概括
作为OCT2/MATE1调节剂的西米蒂丁和甲胺可以安全地与三里丁/蒂皮拉西尔同时使用. 这项研究没有发现临床相关的药物相互作用,影响癌症患者的trifluridine暴露.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 临床药房 临床药房
背景情况:
- 特里弗鲁里丁/蒂皮拉西尔用于转移性胃癌和结肠直肠癌.
- 它与有机阴离子载体2 (OCT2) 和多药物和毒素挤出蛋白1 (MATE1) 相互作用.
- 与其他OCT2/MATE1调节剂存在潜在的药物相互作用 (DDI).
研究的目的:
- 为了评估cimetidine (OCT2/MATE1抑制剂) 和metformin (OCT2/MATE1基质) 对trifluridine的药理动力学影响.
- 为了确定是否同时使用导致临床相关的DDI.
主要方法:
- 这是一项涉及18名癌症患者的三阶段交叉研究.
- 患者接受了单独的trifluridine/tipiracil,与甲福林,或与cimetidine.
- 三氨酸暴露 (AUC) 是主要终点; >30%的变化被认为是临床相关的.
主要成果:
- 甲素没有显著改变三里丁的暴露 (-12.6%,p=0.045).
- 齐米蒂丁显著增加了三里丁的暴露率 (+18.0%,p=0.004),但低于临床相关性值.
- 特里弗鲁里丁/蒂皮拉西尔没有影响甲福林的最低度.
结论:
- 同时使用西米蒂丁或甲福林与三里丁/蒂皮拉西尔不太可能导致临床相关的DDI.
- 这表明,在癌症患者中,这些药物的同时使用是安全的.
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