基因型和药监督对自闭症谱系障碍的影响:自然主义研究与极端表型分析
Pura Ballester1, Cristina Espadas2, Susana Almenara3,4
1Pharmacology Department, Pharmacy Degree, San Antonio Catholic University, 30107 Murcia, Spain.
Pharmaceuticals (Basel, Switzerland)
|July 29, 2023
概括
在自闭症谱系障碍 (ASD) 中,细胞染色体P450 (CYP) 2D6酶的基因定型可以提高药物安全性. 了解CYP2D6表型有助于预测不良事件,特别是在多处方的情况下.
科学领域:
- 药物基因组学 药物基因组学
- 神经发育障碍 神经发育障碍
- 临床药理学 临床药理学
背景情况:
- 在自闭症谱系障碍 (ASD) 中长期使用心理药物学缺乏安全性和耐受性证据.
- 细胞染色体P450 (CYP) 2D6基因定型可以识别有不良药物反应风险的个体.
- 常见的ASD药物如Risperidone和aripiprazole是通过CYP2D6代谢的.
研究的目的:
- 研究CYP2D6表型对ASD成年人心理药物耐受性的影响.
- 分析CYP2D6遗传变异与该人群中不良事件 (AE) 之间的关系.
- 评估多药对AEs与CYP2D6表型有关的影响.
主要方法:
- 一个自然主义的观察性研究,使用本地药监系统.
- 从电子健康记录和纸质登记册中识别AE.
- 对CYP2D6等位基因的基因型鉴定和拷贝数变异以确定表型 (PM,IM,NM,UM).
- 收集社会人口统计数据,并发病症和精神药物学处方.
主要成果:
- 包括71名患有自闭症的成年人 (平均年龄30岁,82%是男性);45%具有正常的CYP2D6 (NM) 表型.
- 在CYP2D6超快代谢者 (UM) 中,多药性率最高.
- CYP2D6中间代谢剂 (IM) 显示神经和精神病AEs的发生率最高,由CYP2D6抑制剂加剧.
结论:
- 为了提高ASD成年人药物安全性,CYP2D6的药物基因组学至关重要.
- 监测抗精神病药物处方以及遗传特征可以预防AEs.
- 了解CYP2D6表型对于管理精神药物学多药治疗和改善患者治疗结果至关重要.
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