在体外评估沙利德胺对药物相互作用潜力的评估
Philip G Kasprzyk1, Larry Tremaine2, Odette A Fahmi3
1DoubleRainbow Biosciences Inc., Lexington, MA 02421, USA.
Nutrients
|September 9, 2023
概括
生物工程的salidroside是Rhodiola rosea的一个组成部分,被评估了药物相互作用风险. 研究表明,在预测度下,与CYP450,MAO酶或OATP载体没有显著的相互作用,支持其安全的同时使用.
科学领域:
- 药理学 药理学是指药理学的学科.
- 药物代谢和药物相互作用
- 植物化学 植物化学
背景情况:
- 罗迪奥拉含有各种植物化学物质,之前的研究表明基于酶抑制和临床前数据的潜在药物相互作用 (DDI) 风险.
- 罗迪奥拉成分的变化使得准确的DDI风险评估变得复杂.
研究的目的:
- 为了评估生物工程,自然相同的salidroside的DDI潜力.
- 评估沙利德对主要的P450 (CYP450) 酶,单胺氧化酶 (MAO-A和MAO-B) 和有机阴离子载体多 (OATP) 的抑制作用.
主要方法:
- 在体外抑制试验中,使用人肝显微体进行CYP450酶分析.
- 基于肝细胞的测定以确定CYP450酶诱导.
- 对MAO-A和MAO-B抑制进行重组酶测定.
- 用转染的HEK293细胞进行基于细胞的测定,以评估OATP载体抑制.
主要成果:
- 生物工程化没有抑制主要的CYP450酶 (CYP1A2,2B6,2C8,2C9,2C19,2D6,3A4) 或诱导CYP1A2,CYP2B6和CYP3A4的度超过预测的治疗水平 (<2μM).
- 沙利德胺没有显示对MAO-A和MAO-B的抑制潜力.
- 没有观察到OATP1B1和OATP1B3载体的抑制.
结论:
- 生物工程萨利德化物显示,通过CYP450,MAO或OATP通路发生药物相互作用的风险较低.
- 这些发现支持使用salidroside与通过这些途径代谢的药物的安全并发使用.
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