细胞染色体P450 2D6 较差的代谢剂和风胺治疗失败:一年的纵向研究
Marianna Piras1, Setareh Ranjbar2, Séverine Crettol1
1Unit of Pharmacogenetics and Clinical Psychopharmacology, Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, University of Lausanne, Prilly, Switzerland.
Clinical pharmacology and therapeutics
|May 12, 2025
概括
患有 CYP2D6 代谢器状况不佳的患者更有可能从瑞斯佩里转换. 这种增加的风险在三个月后变得显著,并在治疗的第一年增长.
科学领域:
- 药物基因组学 药物基因组学
- 临床药理学 临床药理学
- 精神病学是一个精神病学.
背景情况:
- 细胞染色体P450 2D6 (CYP2D6) 对于代谢大约20%的处方药物至关重要,包括瑞斯佩里.
- 以前的研究表明,在CYP2D6低代谢者 (PMs) 中,从RISPERIDONE切换抗精神病药物的可能性更高.
- 这些先前的研究没有考虑在转换发生之前的治疗持续时间.
研究的目的:
- 分析与CYP2D6代谢器状态和治疗持续时间有关的RISPERIDONE治疗失败,定义为转换药物.
- 量化与其他表型相比,CYP2D6 PMs随时间的推移而从RISPERIDONE转换的风险.
- 评估药物遗传测试对治疗结果的潜在影响.
主要方法:
- 来自PsyMetab队列的515名患者的分析.
- 使用卡普兰-梅尔估计与日志等级测试和考克斯多变量回归.
- 检查了RISPERIDONE与PALIPERIDONE的比率以及切换时间的数据.
主要成果:
- 在CYP2D6的PM中,RISPERIDONE与PALIPERIDONE的比率显著更高 (中位数为2.78与0.14).
- 一年后,70%的PM从RISPERIDONE切换到其他表型的42% (P=0.026).
- 随着时间的推移,PMs的切换风险显著增加,在3个月后变得具有统计学意义,并在12个月后升级 (HR 16.3,P=0.001).
结论:
- CYP2D6 PM 状态与从RISPERIDONE 治疗转换的风险增加有关.
- 这种高风险取决于时间,在3个月后出现,并在一年内大幅增长.
- 药物遗传学概况可以指导治疗决策,可能减少药物切换.
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