索拉尼丁衍生的CYP2D6表型化揭示了多种药物治疗的老年患者的表转化
Jens Andreas Sarömba1, Julian Peter Müller1, Jolanta Tupiec1
1Institute of Clinical Pharmacology, University Hospital RWTH Aachen, Aachen, North Rhine-Westphalia, Germany.
这项研究使用饮食衍生生物标志物来确定老年患者中细胞染色体P450 2D6 (CYP2D6) 活性的现象转化. 这种方法可以帮助个性化药物处方复杂的患者群体.
科学领域:
- 药物基因组学 药物基因组学
- 临床化学 临床化学
背景情况:
- 转化,预测和实际药物代谢之间的不匹配,阻碍了个性化医疗.
- 老年患者通常具有多病症和多药性,增加了由于药物代谢变化的不良药物事件的风险.
研究的目的:
- 为了检测和量化老年人,使用特定的索拉尼丁代谢物作为细胞染色体P450 2D6 (CYP2D6) 活性的生物标志物的多病症患者的表转化.
- 评估这些生物标志物的实用性在高多药环境中.
主要方法:
- 从接受医生咨询的老年患者收集血液样本和药物数据.
- 量化索拉尼丁及其代谢物 (包括3,4-二次索拉尼丁-3,4-二氧酸[SSDA]) 使用液体染色学/并联质谱法用于CYP2D6表型化.
- 根据基因型鉴定分配CYP2D6活性评分 (AS),并将其与表型鉴定结果进行比较.
主要成果:
- 分析了88名老年患者 (平均年龄83岁,70.5%为女性) 的数据,平均服用15种药物.
- SSDA/索拉尼丁代谢比与基因定型衍生的AS显著相关 (P<.001),有效地识别了弱CYP2D6代谢者.
- 每个额外的CYP2D6基质/抑制剂在调整共变量 (R2 = 0.242) 后,在具有功能性CYP2D6变异的患者中,每次额外的CYP2D6基质/抑制剂都将预测的AS降低了0.53.
结论:
- 对CYP2D6表型的饮食衍生生物标志物可以阐明老年患者多病症和多药性患者的表型转化.
- 这些发现支持开发一种床边方法来测量CYP2D6活性,这对于复杂患者群体的个性化药物处方至关重要.
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