The Effects of Fluvoxamine on the Steady-State Plasma Concentrations of Escitalopram and Desmethylescitalopram in Depressed Japanese Patients

摘要

Background:The aim of this study was to determine the impact of fluvoxamine, an inhibitor of Cytochrome P450 (CYP) 2C19 (CYP2C19), on the pharmacokinetics of escitalopram, a substrate of CYP2C19.Methods:Thirteen depressed patients initially received a 20-mg/d dose of escitalopram alone. Subsequently, a 50-mg/d dose of fluvoxamine was administered because of the insufficient efficacy of escitalopram. Plasma concentrations of escitalopram and desmethylescitalopram were quantified using high-performance liquid chromatography before and after fluvoxamine coadministration. The QT and corrected QT (QTc) intervals were measured before and after fluvoxamine coadministration.Results:Fluvoxamine significantly increased the plasma concentrations of escitalopram (72.3 36.9 ng/mL versus 135.2 +/- 79.7 ng/mL, P < 0.01) but not those of desmethylescitalopram (21.5 +/- 7.0 ng/mL versus 24.9 +/- 12.0 ng/mL, no significance [ns]). The ratios of desmethylescitalopram to escitalopram were significantly decreased during fluvoxamine coadministration (0.37 +/- 0.21 versus 0.21 +/- 0.10, P < 0.01). The CYP2C19 genotype did not fully explain the degree of the change. Fluvoxamine coadministration did not change the QT or QTc intervals.Conclusions:The results of this study suggest that adjunctive treatment with fluvoxamine increases the concentration of escitalopram. The QTc interval did not change in this condition.