Department of Psychiatry, Psychotherapy and Psychosomatics, JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany; Alexianer Krankenhaus Aachen, Germany.
Department of Psychiatry, Psychotherapy and Psychosomatics, JARA - Translational Brain Medicine, RWTH Aachen University, Aachen, Germany; University Hospital of Psychiatry, Bern, Switzerland.
Prog Neuropsychopharmacol Biol Psychiatry. 2018 Jul 13;85:116-121. doi: 10.1016/j.pnpbp.2018.04.014. Epub 2018 Apr 25.
Venlafaxine and the atypical antipsychotic quetiapine are often administered concomitantly. Both drugs share several metabolic hepatic pathways. However, pharmacokinetic interactions between venlafaxine and quetiapine have not been studied yet. A therapeutic drug monitoring database containing serum concentrations of venlafaxine (VEN) and its active metabolite O-desmethylvenlafaxine (ODVEN) was analyzed. Two groups of patients were compared: venlafaxine monotherapy V (n = 153) and co-medication with quetiapine, V (n = 71). Serum concentrations of VEN, ODVEN, and active moiety, AM (VEN + ODVEN), metabolite to parent compound ratio (ODVEN/VEN) and dose adjusted serum concentrations were compared using non-parametrical tests without information on CYP2D6 genotype. The two groups did not differ in terms of the daily dosage of venlafaxine, age, or sex. Median serum concentrations in the quetiapine group showed significantly, 15.8% and 29.3% higher values for AM and ODVEN (p = 0.002, Cohen's d = 0,41; p = 0.003, d = 0,44), respectively. Dose adjusted serum concentrations of active moiety and ODVEN revealed comparable differences (p = 0.038, d = 0,32; p = 0.015, d = 0,28) with significantly higher values in the co-medicated group. Significantly higher values for ODVEN and AM suggest a reduced clearance of ODVEN and active moiety when quetiapine is co-administered. This may be a consequence of a reduced metabolism of venlafaxine to the inactive metabolite N-desmethylvenlafaxine via CYP3A4, the main metabolizing enzyme for quetiapine, and a shift towards a higher proportion of the active metabolite ODVEN. Therapeutic drug monitoring is recommended in the case of co-medication to ensure clinical efficacy and patient safety. Although the increase of AM is moderate, we consider it relevant for clinicians given the prevalence of concomitant medication of quetiapine and venlafaxine.
文拉法辛和非典型抗精神病药喹硫平常合并使用。这两种药物都有几个共同的代谢肝途径。然而，文拉法辛和喹硫平之间的药代动力学相互作用尚未被研究过。分析了一个包含文拉法辛（VEN）及其活性代谢物 O-去甲文拉法辛（ODVEN）血清浓度的治疗药物监测数据库。比较了两组患者：文拉法辛单药治疗 V（n=153）和合并喹硫平治疗 V（n=71）。使用非参数检验比较 VEN、ODVEN 和活性部分 AM（VEN+ODVEN）、代谢产物与母体化合物的比值（ODVEN/VEN）和剂量调整后的血清浓度，而不提供 CYP2D6 基因型的信息。两组患者在文拉法辛的日剂量、年龄或性别方面没有差异。喹硫平组的血清浓度中位数分别显著高出 AM 和 ODVEN 15.8%和 29.3%（p=0.002，Cohen's d=0.41；p=0.003，d=0.44）。活性部分和 ODVEN 的剂量调整后血清浓度显示出类似的差异（p=0.038，d=0.32；p=0.015，d=0.28），合并用药组的数值明显更高。ODVEN 和 AM 值较高表明，当喹硫平合并使用时，ODVEN 和活性部分的清除率降低。这可能是由于 CYP3A4（喹硫平的主要代谢酶）减少了文拉法辛向无活性代谢物 N-去甲文拉法辛的代谢，以及向活性代谢物 ODVEN 的比例增加所致。当合并用药时，建议进行治疗药物监测，以确保临床疗效和患者安全。虽然 AM 的增加是适度的，但考虑到喹硫平和文拉法辛合并用药的普遍性，我们认为这对临床医生来说是相关的。
