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Impact of CYP2C19 Genotype on Escitalopram Exposure and Therapeutic Failure: A Retrospective Study Based on 2,087 Patients
American Journal of Psychiatry ( IF 17.7 ) Pub Date : 2018-01-12 , DOI: 10.1176/appi.ajp.2017.17050550
Marin M. Jukić 1 , Tore Haslemo 1 , Espen Molden 1 , Magnus Ingelman-Sundberg 1
Affiliation  

Objective:

The antidepressant escitalopram is predominantly metabolized by the polymorphic CYP2C19 enzyme. The authors investigated the effect of CYP2C19 genotype on exposure and therapeutic failure of escitalopram in a large patient population.

Method:

A total of 4,228 escitalopram serum concentration measurements from 2,087 CYP2C19-genotyped patients 10–30 hours after drug intake were collected retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo. The patients were divided into subgroups based on CYP2C19 genotype: those carrying inactive (CYP2C19Null) and gain-of-function (CYP2C19*17) variant alleles. The between-subgroup differences in escitalopram exposure (endpoint: dose-harmonized serum concentration) and therapeutic failure (endpoint: switching to another antidepressant within 1 year after the last escitalopram measurement) were evaluated by multivariate mixed model and chi-square analysis, respectively.

Results:

Compared with the CYP2C19*1/*1 group, escitalopram serum concentrations were significantly increased 3.3-fold in the CYP2C19Null/Null group, 1.6-fold in the CYP2C19*Null/*1 group, and 1.4-fold in the CYP2C19Null/*17 group, whereas escitalopram serum concentrations were significantly decreased by 10% in the CYP2C19*1/*17 group and 20% in the CYP1C19*17/*17 group. In comparison to the CYP2C19*1/*1 group, switches from escitalopram to another antidepressant within 1 year were 3.3, 1.6, and 3.0 times more frequent among the CYP2C19Null/Null, CYP2C19*1/*17, and CYP1C19*17/*17 groups, respectively.

Conclusions:

The CYP2C19 genotype had a substantial impact on exposure and therapeutic failure of escitalopram, as measured by switching of antidepressant therapy. The results support the potential clinical utility of CYP2C19 genotyping for individualization of escitalopram therapy.



中文翻译:

的影响CYP2C19基因型对艾司西酞普兰暴露和治疗失败:回顾性研究基于对2087例

客观的:

抗抑郁药依他普仑主要由多态性CYP2C19酶代谢。作者研究了CYP2C19基因型对艾司西酞普兰在大量患者中的暴露和治疗失败的影响。

方法:

在奥斯陆的Diakonhjemmet医院的药物监测数据库中,回顾性分析了服用药物后10-30小时从2,087位CYP2C19基因型患者中收集的4,228份依西酞普兰的血清浓度。根据CYP2C19基因型将患者分为亚组:那些携带无效(CYP2C19 Null)和功能获得(CYP2C19 * 17)等位基因的患者。分别通过多元混合模型和卡方分析评估了依西酞普兰暴露(终点:剂量一致的血清浓度)和治疗失败(终点:在最后一次依西酞普兰测量后1年内改用另一种抗抑郁药)之间的亚组间差异。

结果:

与所比较的CYP2C19 * 1 / * 1组,依他普仑血清浓度显著增加3.3倍的在CYP2C19空/空组中,在1.6倍CYP2C19 * NULL / * 1组,并在1.4倍CYP2C19/ * 17组,而CYP2C19 * 1 / * 17组的依西酞普兰血清浓度显着降低10 %,而CYP1C19 * 17 / * 17组则降低20%。与CYP2C19 * 1 / * 1组相比,在1年内从escitalopram切换至另一种抗抑郁药的频率是CYP2C19 Null / Null,CYP2C19 * 1 / * 173.3、1.6和3.0倍CYP1C19 * 17 / * 17组。

结论:

CYP2C19基因型对曝光和依他普仑的治疗失败有实质性的影响,如通过抗抑郁药治疗的切换测量。该结果支持CYP2C19基因分型对依他普仑治疗个体化的潜在临床效用。

更新日期:2018-05-01
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