Sertraline is an (SSRI-)antidepressant metabolized by the polymorphic CYP2C19 enzyme. The aim of this study was to investigate the impact of CYP2C19 genotype on the serum concentrations of sertraline in a large patient population. Second, the proportions of patients in the various CYP2C19 genotype-defined subgroups obtaining serum concentrations outside the therapeutic range of sertraline were assessed. A total of 2190 sertraline serum concentration measurements from 1202 patients were included retrospectively from the drug monitoring database at Diakonhjemmet Hospital in Oslo. The patients were divided into CYP2C19 genotype-predicted phenotype subgroups, i.e. normal (NMs), ultra rapid (UMs), intermediate (IMs), and poor metabolisers (PMs). The differences in dose-harmonized serum concentrations of sertraline and N-desmethylsertraline-to-sertraline metabolic ratio were compared between the subgroups, with CYP2C19 NMs set as reference. The patient proportions outside the therapeutic concentration range were also compared between the subgroups with NMs defined as reference. Compared with the CYP2C19 NMs, the sertraline serum concentration was increased 1.38-fold (95% CI 1.26-1.50) and 2.68-fold (95% CI 2.16-3.31) in CYP2C19 IMs and PMs, respectively (p < 0.001), while only a marginally lower serum concentration (-10%) was observed in CYP2C19 UMs (p = 0.012). The odds ratio for having a sertraline concentration above the therapeutic reference range was 1.97 (95% CI 1.21-3.21, p = 0.064) and 8.69 (95% CI 3.88-19.19, p < 0.001) higher for IMs and PMs vs. NMs, respectively. CYP2C19 IMs and PMs obtain significantly higher serum concentrations of sertraline than NMs. Based on the relative differences in serum concentrations compared to NMs, dose reductions of 60% and 25% should be considered in PMs and IMs, respectively, to reduce the risk of sertraline overexposure in these patients.

中文翻译：

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CYP2C19 基因型对 1200 名斯堪的纳维亚患者舍曲林暴露的影响。

舍曲林是一种 (SSRI-) 抗抑郁药，由多态性 CYP2C19 酶代谢。本研究的目的是调查 CYP2C19 基因型对大量患者人群中舍曲林血清浓度的影响。其次，评估了各种 CYP2C19 基因型定义亚组中血清浓度超出舍曲林治疗范围的患者比例。从奥斯陆 Diakonhjemmet 医院的药物监测数据库中回顾性地纳入了来自 1202 名患者的总共 2190 次舍曲林血清浓度测量值。患者被分为CYP2C19基因型预测的表型亚组，即正常（NMs）、超快速（UMs）、中间（IMs）和低代谢者（PMs）。比较亚组间舍曲林的剂量协调血清浓度和 N-去甲基舍曲林与舍曲林代谢比的差异，以 CYP2C19 NMs 作为参考。还在将 NM 定义为参考的亚组之间比较治疗浓度范围之外的患者比例。与 CYP2C19 NMs 相比，CYP2C19 IMs 和 PMs 中舍曲林血清浓度分别增加了 1.38 倍（95% CI 1.26-1.50）和 2.68 倍（95% CI 2.16-3.31）（p < 0.001），而只有在 CYP2C19 UM 中观察到略低的血清浓度 (-10%) (p = 0.012)。IM 和 PM 与 NM 相比，舍曲林浓度高于治疗参考范围的优势比为 1.97（95% CI 1.21-3.21，p = 0.064）和 8.69（95% CI 3.88-19.19，p < 0.001），分别。CYP2C19 IMs 和PMs 获得比NMs 显着更高的舍曲林血清浓度。基于与 NM 相比血清浓度的相对差异，应考虑将 PM 和 IM 的剂量分别降低 60% 和 25%，以降低这些患者舍曲林过度暴露的风险。