文拉法辛与细胞色素P450酶的相关性研究进展

文拉法辛是具有5-HT和NE双重再摄取抑制作用的新型抗抑郁药,与文拉法辛代谢密切相关的2种酶是CYP3A4和CYP2D6。CYP2D6将其生物转化为主要的活性代谢产物——O-去甲基文拉法辛（ODV）,同时CYP3A4将文拉法辛转化为非活性代谢产物N-去甲基文拉法辛（NDV）。在常规治疗剂量下文拉法辛对于CYP3A4缺乏明显的诱导或抑制作用。而CYP2D6的活性直接影响文拉法辛和ODV的代谢和浓度,由于CYP2D6存在着基因遗传多态性,不同表型有着不同的文拉法辛代谢能力,而慢代谢者更易发生不良反应。研究证实文拉法辛与ODV的浓度比log（VENL／ODV）可作为异常代谢的指标,较简便地发现大多数异常基因型患者。

Research developments about the interaction of venlafaxine with cytochrome P450

Venlafaxine is a new antidepressant drug which is a mixed serotonin and noradrena- line reuptake inhibitor,CYP3A4 and CYP2D6 are involved in the metabolism of venlafaxine.Venlafaxine is biotransformed by the cytochrome P450(CYP)isozyme 2D6 to its major metabolite,O-desmethylven- lafaxine(ODV),and in parallel to N-desmethylvenlafaxine(NDV)by CYP3A4.At clinically relevant dosages,venlafaxine lacks appreciable CYP3A4 inductive or inhibitory activity.But the activity of CYP2D6 directly influences the metabolism and concentration in serum of venlafaxine and ODV.Due to the genetic polymorphism of CYP2D6,different phenotypes have different metabolic capacities for ven- lafaxine.Moreover,the Poor metabolizer(PM)increases the risk of side effects.Some research demon- strates that the metabolic ratio of venlafaxine and ODVlog(VENL/ODV)]may serve as an indication of aberrant metabolism.It could help us to detect the most of aberrant genotypes more easily.