特比萘芬和伏立康唑对抗抑郁药文拉法辛药代动力学的影响。
Effect of terbinafine and voriconazole on the pharmacokinetics of the antidepressant venlafaxine.
作者信息
Hynninen V-V, Olkkola K T, Bertilsson L, Kurkinen K, Neuvonen P J, Laine K
机构信息
Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku University Hospital, Turku, Finland.
出版信息
Clin Pharmacol Ther. 2008 Feb;83(2):342-8. doi: 10.1038/sj.clpt.6100311. Epub 2007 Aug 8.
This study investigated the effect of terbinafine and voriconazole on the pharmacokinetics of venlafaxine in healthy volunteers. Plasma concentrations of venlafaxine and O-desmethylvenlafaxine (ODV) were measured after ingestion of 75 mg venlafaxine without pretreatment (control), after terbinafine pretreatment, or after voriconazole pretreatment. During the terbinafine phase, the area under the plasma concentration-time curve (AUC(0-infinity)) of venlafaxine was on average 490% (P<0.001) and that of ODV 57% (P<0.001) of the corresponding control value. Terbinafine decreased the AUC(0-infinity) ratio of ODV over venlafaxine by 82% (P<0.001). Voriconazole slightly increased the sum of AUC(0-infinity) of venlafaxine plus AUC(0-infinity) of ODV (active moiety) by 31% (P<0.001). The most likely mechanism for the interaction between terbinafine and venlafaxine is the inhibition of CYP2D6-mediated O-demethylation of venlafaxine, whereas the minor effects of voriconazole are probably due to the inhibition of CYP3A4-, CYP2C9-, or CYP2C19-mediated metabolism of venlafaxine.
本研究调查了特比萘芬和伏立康唑对健康志愿者体内文拉法辛药代动力学的影响。在未进行预处理（对照）、经特比萘芬预处理或经伏立康唑预处理后，给予75 mg文拉法辛，然后测量文拉法辛和O-去甲基文拉法辛（ODV）的血浆浓度。在特比萘芬阶段，文拉法辛的血浆浓度-时间曲线下面积（AUC(0-∞)）平均为相应对照值的490%（P<0.001），ODV为57%（P<0.001）。特比萘芬使ODV与文拉法辛的AUC(0-∞)比值降低了82%（P<0.001）。伏立康唑使文拉法辛的AUC(0-∞)与ODV（活性部分）的AUC(0-∞)之和略有增加，增幅为31%（P<0.001）。特比萘芬与文拉法辛相互作用最可能的机制是抑制CYP2D6介导的文拉法辛O-去甲基化，而伏立康唑的轻微影响可能是由于抑制了CYP3A4、CYP2C9或CYP2C19介导的文拉法辛代谢。
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