0000000000014113
AUTHOR
Mohamed E. E. Shams
Melperone is an Inhibitor of the CYP2D6 Catalyzed O-demethylation of Venlafaxine
INTRODUCTION Melperone, a butyrophenone neuroleptic, is frequently used for its sleep-inducing properties. Despite its common use for more than 30 years, it is not yet characterized regarding its effects on cytochrome P450 s (CYPs). In an open pilot study, effects of melperone on the steady-state blood levels of venlafaxine, a recently introduced serotonin- and noradrenaline reuptake inhibiting antidepressant, were assessed. METHODS The dose-corrected serum concentrations of venlafaxine and O-desmethylvenlafaxine were analyzed retrospectively in a therapeutic drug-monitoring (TDM) database comprising 94 patients. In addition, three patients received venlafaxine and melperone concomitantly a…
Therapeutic Drug Monitoring of the Antidepressant Mirtazapine and Its N-Demethylated Metabolite in Human Serum
Mirtazapine is a novel antidepressant that acts by enhancing serotonergic and noradrenergic neurotransmission. Because very little is known about serum concentrations in relation to clinical effects, the use of therapeutic drug monitoring is so far unclear. A rapid automated HPLC method with fluorescence detection was developed for routine quantification of mirtazapine and its demethylated metabolite N-desmethylmirtazapine in human serum. The precision of the method was suitable because the day-to-day (n = 7) coefficient of variation (CV) of mirtazapine was 9.8, 4.2, and 5.1% for concentrations of 10, 40, and 80 ng/mL, respectively, and the CV for N-desmethylmirtazapine were 11.6, 10.3, and…
CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine.
SUMMARY Background: Venlafaxine (V) is a mixed serotoninand noradrenaline reuptake inhibitor used as afirst-line treatment of depressive disorders. It ismetabolized primarily by the highly polymorphiccytochrome P450 (CYP) enzyme CYP2D6 to yielda pharmacologically active metabolite, O-des-methylvenlafaxine (ODV), and to a lesser extentby CYP3A4, to yield N-desmethylvenlafaxine(NDV).Objectives: The aim of this study was to assesswhether the O-demethylation phenotype of V hasan impact on the pharmacokinetics and clinicaloutcome.Method: In 100 patients treated with V, serumconcentrations of V, ODV and NDV and theratios of concentrations ODV/V as a measure ofO-demethylation were determined. Indiv…