在CYP2C19基因型的健康志愿者中,由于药物相互作用而导致的光转化
Kenza Abouir1,2, Nadia Exquis1, Yvonne Gloor1,2
1Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Genève 14, Switzerland.
Clinical pharmacology and therapeutics
|July 30, 2024
概括
药物相互作用可以改变药物代谢,在80%以上的个体中引起表转化. 基因和测量的表型对于预测药物反应和预防不良事件至关重要.
科学领域:
- 药物基因组学 药物基因组学
- 药物新陈代谢 药物新陈代谢
- 临床药理学 临床药理学
背景情况:
- 药物反应的变化需要通过基因测试来确定表型,以调整剂量.
- 同时服用药物的药物相互作用可能会导致表转化,导致预测和观察到的药物代谢表型之间的差异.
研究的目的:
- 为了前性地评估暴露于CYP2C19抑制剂的基因型健康志愿者中CYP2C19变异的风险.
- 评估遗传变异和特定抑制剂 (沃里可纳,黄) 对CYP2C19转化现象的影响.
主要方法:
- 这是一项前性探索性研究,涉及三组基因型的健康志愿者 (CYP2C19 g-RM,g-NM,g-IM).
- 志愿者接受了单独的奥梅普拉 (CYP2C19基质) 和CYP2C19抑制剂 (沃里科纳或弗卢沃胺) 的治疗.
- 通过比较抑制剂服药前后的表型,以及基因型-表型重新分类来评估表型转化.
主要成果:
- 转化发生在80%以上的健康志愿者身上,因基因型和抑制剂而异.
- 在具有不同基因型的CYP2C19中间代谢剂之间观察到代谢比率的显著差异 (*1/*2 vs. *2/*17).
- 在暴露于抑制剂后,其他组 (p-NM,p-IM,p-PM) 发生了100%的快速代谢器 (p-RM) 变异和显著的表型切换.
结论:
- 遗传变异显著影响易受CYP2C19变异的脆弱性.
- 基因型定型和表型定型对于准确预测药物反应和管理潜在的表型转化都很重要.
- 同时服用作为CYP2C19抑制剂的药物可以显著改变药物代谢表型.
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