Scherf-Clavel Maike, Weber Heike, Unterecker Stefan, Frantz Amelie, Eckert Andreas, Reif Andreas, Deckert Jürgen, Hahn Martina
Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, 97080 Würzburg, Germany.
Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, 60528 Frankfurt, Germany.
Pharmacopsychiatry. 2024 Mar;57(2):69-77. doi: 10.1055/a-2248-6924. Epub 2024 Feb 14.
CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status.
Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PC, PC) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine.
There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram.
PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.
由基因型定义的CYP2D6和CYP2C19功能状态会因药代动力学相互作用导致的表型转换（PC）而受到调节。截至目前，尚无关于PC对CYP2C19功能状态影响大小的数据。本研究的主要目的是调查PC对CYP2C19功能状态的影响。
采用两种不同的校正方法（PC、PC）以及文拉法辛、阿米替林、米氮平、舍曲林、艾司西酞普兰、利培酮和喹硫平的血清浓度和代谢物与母体比例，对两个患者队列（共n = 316；44.2±15.4岁）进行CYP2C19功能酶状态调查。
CYP2C19正常代谢者数量减少，慢代谢者数量增加。在对年龄、性别以及在阿米替林、文拉法辛和利培酮的情况下对CYP2D6功能酶状态进行校正后，观察到CYP2C19表型/功能酶状态与阿米替林、舍曲林和艾司西酞普兰的血清浓度之间存在关联。
CYP2C19的PC改变了表型，但并未改善与血清浓度的相关性。然而，仅少数患者接受了CYP2C19的干扰剂。仍缺乏大量患者的研究，因此，无法确定是否存在微小差异以及使用哪种校正方法。目前，PC在接受影响CYP2C19药物治疗的个体患者中具有相关性，例如埃索美拉唑。为确保这些患者有足够的血清浓度，本研究建议使用治疗药物监测。
