Effect of terbinafine and voriconazole on the pharmacokinetics of the antidepressant venlafaxine.
Clin Pharmacol Ther
; 83(2): 342-8, 2008 Feb.
Article
de En
| MEDLINE
| ID: mdl-17687273
ABSTRACT
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.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Pyrimidines
/
Triazoles
/
Antidépresseurs de seconde génération
/
Cyclohexanols
/
Antienzymes
/
Inhibiteurs du cytochrome P-450 CYP2D6
/
Naphtalènes
Type d'étude:
Clinical_trials
/
Prognostic_studies
Limites:
Adult
/
Humans
/
Male
Langue:
En
Journal:
Clin Pharmacol Ther
Année:
2008
Type de document:
Article
Pays d'affiliation:
Finlande