对CYP2D6基因型对杜洛克赛丁血清度的影响
Kristine Hole1,2, Sofie Gangsø1,2, Åsa Tonette Jensstuen1,2
1Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.
Basic & clinical pharmacology & toxicology
|October 21, 2023
概括
细胞染色体P450 (CYP) 2D6的低代谢者具有双倍的杜洛西丁度. 患有 CYP2D6 代谢不良表型的老年女性面临高药水平的三倍风险.
科学领域:
- 药物基因组学 药物基因组学
- 药物新陈代谢 药物新陈代谢
背景情况:
- 杜洛西丁是一种抗抑郁药,由CYP1A2和CYP2D6酶代谢.
- 药物反应的个体变异性需要了解对新陈代谢的遗传影响.
研究的目的:
- 为了研究CYP2D6遗传变异对杜洛西丁血清度的影响.
- 在分析CYP2D6基因型和duloxetine水平之间的关系时,要根据年龄和性别进行调整.
主要方法:
- 从治疗药物监测服务中对患者的回顾性分析.
- 多重线性回归评估CYP2D6基因型,年龄和性别对杜洛西丁度与剂量 (C/D) 比率的影响.
- 分类为CYP2D6表型子组:低 (PMs),中等 (IMs),正常 (NMs) 和超快 (UMs) 的代谢者.
主要成果:
- 与正常代谢剂 (NMs) 相比, CYP2D6 代谢较差者 (PMs) 的duloxetine C/D 比率高出 95% (p=0.009).
- 65岁及以上的患者的C/D比率比年轻人高56% (p=0.01).
- 女性的C/D比率比男性高46% (p=0.04).
结论:
- 在标准剂量下,CYP2D6 PM表型与duloxetine度增加两倍有关.
- 患有CYP2D6PM的老年女性患上杜洛西丁水平升高的风险较高,与年轻的男性NMS相比,可能达到C/D比率高三倍.
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