基因型CYP2C19对因同时服用药物而导致的表转化的影响
Laura M de Jong1, Soukayna Boussallami1, Elena Sánchez-López2
1Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden, Netherlands.
Frontiers in pharmacology
|June 26, 2023
概括
药物相互作用可以改变预测的药物代谢表型,影响药物遗传学. 这项研究表明,CYP2C19基因型影响药物相互作用的结果,基底活性和疾病因素在转化中起着关键作用.
科学领域:
- 药物遗传学 药物遗传学
- 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:
- 药物遗传学指导的处方根据遗传特征调整药物剂量.
- 药物-药物相互作用 (DDI) 可能导致表转化,导致预测和观察到的药物代谢表型之间的差异.
- CYP2C19是参与许多药物的代谢的关键酶.
研究的目的:
- 调查CYP2C19基因型对依赖CYP2C19的DDI的影响.
- 评估基因型预测和观察到的CYP2C19表型之间的一致性.
- 评估DDI对不同基因型中CYP2C19活性的影响.
主要方法:
- 在40个人类肝脏样本中对CYP2C19变体 (*2, *3, *17) 的基因定型.
- 评估CYP2C19活性,使用微小分量的S-美芬因代谢.
- 模拟DDI通过同时暴露微粒对CYP2C19抑制剂 (流胺,伏利可纳,奥梅普拉,潘托普拉).
主要成果:
- 预测和测量CYP2C19表型之间观察到40%的一致性,这表明显著的表转化.
- 黄素,伏利可纳和奥梅普拉显著抑制了CYP2C19的活性,但潘托普拉却没有.
- DDI对CYP2C19活性的影响因基因型而异,某些基因型更容易受到表转化影响.
结论:
- 基因型间CYP2C19介导的DDI的不同结果主要由基底CYP2C19活性决定.
- CYP2C19基因型可以部分预测这些结果,但与疾病相关的因素,如糖尿病和肝脏疾病也会导致转化.
- 了解表观转化对于准确的药物遗传学解释和优化药物治疗至关重要.
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