Pharmacokinetic drug interactions involving vortioxetine (Lu AA21004), a multimodal antidepressant.
Pharmacokinetic drug interactions involving vortioxetine (Lu AA21004), a multimodal antidepressant.
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DOI：
10.1007/s40261-013-0117-6
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发表时间：
2013-10
影响因子：
3.2
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Chen G;Lee R;Højer AM;Buchbjerg JK;Serenko M;Zhao Z
识别和量化潜在的药物相互作用对于避免或最小化与特定药物组合相关的相互作用诱导的不良事件是重要的。在健康受试者中进行了临床研究，以评价沃替西汀与（Lu AA 21004）和联合用药，包括氟康唑（细胞色素P450 [CYP] 2C 9、CYP 2C 19和CYP 3A抑制剂）、酮康唑（CYP 3A和P-糖蛋白抑制剂），利福平（CYP 2D 6诱导剂）、安非他酮（CYP 2D 6抑制剂和CYP 2B 6底物）、炔雌醇/左炔诺孕酮（CYP 3A底物）和奥美拉唑（CYP 2C 19底物和抑制剂）。试验治疗与参比治疗相关参数的中心值比值（例如，血浆浓度-时间曲线下面积[AUC]和最大血浆浓度[Cmax]）用于评估药代动力学相互作用。沃替西汀联合给药对炔雌醇/左炔诺孕酮或5′-羟基奥美拉唑的AUC或Cmax或安非他酮的AUC无影响;这些中心值比值的90%置信区间在80- 125%范围内。沃替西汀与安非他酮（分别为128%和114%）、氟康唑（分别为46%和15%）和酮康唑（分别为30%和26%）联合给药时，沃替西汀的稳态AUC和Cmax增加，沃替西汀与利福平联合给药时，稳态AUC和Cmax分别降低72%和51%。伴随治疗通常耐受良好;大多数不良事件的严重程度为轻度或中度。当沃替西汀与安非他酮或利福平联合给药时，可能需要调整剂量。本文的在线版本（doi：10.1007/s40261-013-0117-6）包含补充材料，可供授权用户使用。
The identification and quantification of potential drug–drug interactions is important for avoiding or minimizing the interaction-induced adverse events associated with specific drug combinations. Clinical studies in healthy subjects were performed to evaluate potential pharmacokinetic interactions between vortioxetine (Lu AA21004) and co-administered agents, including fluconazole (cytochrome P450 [CYP] 2C9, CYP2C19 and CYP3A inhibitor), ketoconazole (CYP3A and P-glycoprotein inhibitor), rifampicin (CYP inducer), bupropion (CYP2D6 inhibitor and CYP2B6 substrate), ethinyl estradiol/levonorgestrel (CYP3A substrates) and omeprazole (CYP2C19 substrate and inhibitor). The ratio of central values of the test treatment to the reference treatment for relevant parameters (e.g., area under the plasma concentration–time curve [AUC] and maximum plasma concentration [C max]) was used to assess pharmacokinetic interactions. Co-administration of vortioxetine had no effect on the AUC or C max of ethinyl estradiol/levonorgestrel or 5′-hydroxyomeprazole, or the AUC of bupropion; the 90 % confidence intervals for these ratios of central values were within 80–125 %. Steady-state AUC and C max of vortioxetine increased when co-administered with bupropion (128 and 114 %, respectively), fluconazole (46 and 15 %, respectively) and ketoconazole (30 and 26 %, respectively), and decreased by 72 and 51 %, respectively, when vortioxetine was co-administered with rifampicin. Concomitant therapy was generally well tolerated; most adverse events were mild or moderate in intensity. Dosage adjustment may be required when vortioxetine is co-administered with bupropion or rifampicin. The online version of this article (doi:10.1007/s40261-013-0117-6) contains supplementary material, which is available to authorized users.
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