Charlier Corinne, Broly Franck, Lhermitte Michel, Pinto Emmanuel, Ansseau Marc, Plomteux Guy
Clinical Toxicology Laboratory, University Hospital, CHU Sart Tilman, B-4000 Liège, Belgium.
Ther Drug Monit. 2003 Dec;25(6):738-42. doi: 10.1097/00007691-200312000-00014.
Most antidepressants are metabolized by cytochrome P450 (CYP) 2D6, and it is well known that there may be significant interindividual variation in the capacity to metabolize xenobiotics. About 7 to 10% of whites are poor metabolisers (PM), and, on the contrary, about 5% are ultrarapid metabolizers (UM), inducing very different rates in the transformation of antidepressants extensively metabolized by CYP 2D6. CYP 2D6 polymorphism can be a potential risk factor for the development of side effects or a reason for the poor efficacy of the treatment. Various probe drugs may be used for phenotyping CYP 2D6, but genotyping is now available using leukocyte DNA and is independent of concomitant drug use. In this study, we used PCR-based methods for the identification of CYP 2D6 genotypes in 49 patients receiving standard doses of fluoxetine or paroxetine and found that plasma concentration of the antidepressant drugs was significantly correlated with genetic status. In one patient who displayed CYP 2D6 gene duplication (UM), paroxetine plasma concentration was extremely low. In PM fluoxetine-treated patients, drug plasma concentration was significantly higher than that seen in extensive metabolizers.
大多数抗抑郁药由细胞色素P450（CYP）2D6代谢，众所周知，对外源性物质的代谢能力可能存在显著的个体差异。约7%至10%的白人是代谢缓慢者（PM），相反，约5%是超快代谢者（UM），这导致由CYP 2D6广泛代谢的抗抑郁药的转化速率差异很大。CYP 2D6基因多态性可能是副作用发生的潜在危险因素或治疗效果不佳的原因。可使用各种探针药物对CYP 2D6进行表型分析，但现在可通过白细胞DNA进行基因分型，且与同时使用的药物无关。在本研究中，我们采用基于聚合酶链反应（PCR）的方法对49例接受标准剂量氟西汀或帕罗西汀治疗的患者进行CYP 2D6基因型鉴定，发现抗抑郁药的血浆浓度与基因状态显著相关。在1例显示CYP 2D6基因重复（UM）的患者中，帕罗西汀血浆浓度极低。在接受氟西汀治疗的PM患者中，药物血浆浓度显著高于广泛代谢者。
