Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
JARA-Translational Brain Medicine, Aachen, Germany.
Pharmacogenomics J. 2020 Dec;20(6):840-844. doi: 10.1038/s41397-020-0169-y. Epub 2020 Jun 1.
Bupropion is hydroxylated to its primary active metabolite hydroxybupropion by cytochrome P450 enzyme CYP2B6. In vitro data suggest the existence of alternative hydroxylation pathways mediated by the highly polymorphic enzyme CYP2C19. However, the impact of its genetic variants on bupropion metabolism in vivo is still under investigation. We report the case of a 28-year-old male Caucasian outpatient suffering from major depressive disorder who did not respond to a treatment with bupropion. Therapeutic drug monitoring revealed very low serum concentrations of both bupropion and hydroxybupropion. Genotyping identified a heterozygous status for the gain-of-function allele with the genotype CYP2C19*1/*17 predicting enhanced enzymatic activity. The present case shows a reduced bupropion efficacy, which may be explained by a reduced active moiety of bupropion and its active metabolite hydroxybupropion, due to alternative hydroxylation pathways mediated by CYP2C19 in an individual with CYP2C19 rapid metabolizer status. The case report thus illustrates the clinical relevance of therapeutic drug monitoring in combination with pharmacogenetics diagnostics for a personalized treatment approach.
安非他酮主要通过细胞色素 P450 酶 CYP2B6 羟化为其主要活性代谢物羟安非他酮。体外数据表明，存在由高度多态性酶 CYP2C19 介导的替代羟化途径。然而，其遗传变异对体内安非他酮代谢的影响仍在研究中。我们报告了一例 28 岁的白人男性门诊患者，患有重度抑郁症，对安非他酮治疗无反应。治疗药物监测显示，安非他酮和羟安非他酮的血清浓度均非常低。基因分型确定了功能获得性等位基因的杂合状态，基因型 CYP2C19*1/*17 预测酶活性增强。本病例显示安非他酮疗效降低，这可能是由于 CYP2C19 快速代谢型个体中 CYP2C19 介导的替代羟化途径导致安非他酮及其活性代谢物羟安非他酮的活性部分减少所致。该病例报告说明了治疗药物监测与药物遗传学诊断相结合在个体化治疗中的临床相关性。
