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Effect of terbinafine and voriconazole on the pharmacokinetics of the antidepressant venlafaxine.

Author(s): Hynninen VV, Olkkola KT, Bertilsson L, Kurkinen K, Neuvonen PJ, Laine K

Affiliation(s): Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku University Hospital, Turku, Finland. vilhyn@utu.fi

Publication date & source: 2008-02, Clin Pharmacol Ther., 83(2):342-8. Epub 2007 Aug 8.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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.

Page last updated: 2008-03-26

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