在周期性吐综合征中对CYP2C19和CYP2D6进行药基因组测试
Milan Patel1, Omeed Partovi1, Katja Karrento1
1Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Neurogastroenterology and motility
|November 13, 2023
概括
对周期性吐综合征 (CVS) 中的CYP2C19和CYP2D6的药物遗传学测试没有显示与药物不良反应或临床反应的直接联系. 需要进一步的研究,以优化对CVS患者的阿米丁林治疗.
科学领域:
- 药物基因组学 药物基因组学
- 胃肠病学 胃肠病学
- 临床药理学 临床药理学
背景情况:
- 阿米特利普提林 (AT) 是循环吐综合征 (CVS) 的一线治疗方法,但副作用经常限制其使用.
- 目前的剂量依赖于试验和错误,尽管临床药物遗传实施联盟 (CPIC) 的指导方针建议基于AT的基因型剂量.
- 在CYP2C19和CYP2D6酶的遗传变异影响AT代谢.
研究的目的:
- 调查CYP2C19和CYP2D6基因型与药物不良反应 (ADR),临床反应和AT及其代谢物北素的血清度在患有CVS的成年人之间的关联.
- 评估药物遗传检测在管理CVS方面的潜在有用性.
主要方法:
- 试点研究涉及46名被诊断患有CVS的成年人.
- 确定CYP2C19和CYP2D6的基因型.
- 对基因型,副作用,临床反应和血清药物水平之间的相关性进行分析.
主要成果:
- 遗传变异的患病率:33%正常CYP2C19,4%不良,43%超快;61%正常CYP2D6,9%不良,2%超快.
- 在基因型和ADR,临床反应或血清药物度之间没有发现具有统计意义的关联.
- 在CYP2D6基因型和临床反应 (p=0.06) 之间观察到显著性的趋势.
- 药物不良反应发生在46%的患者中,导致28%的患者停药.
结论:
- 值得注意的是,CVS患者的一个显著子组具有功能障碍的CYP2C19和CYP2D6等位基因.
- 需要进行更大规模的前性研究来确认CVS中药基因组测试的临床影响.
- 药基因组测试有可能优化AT疗法,预测ADR,并为CVS提供个性化治疗策略.
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