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

Abstract

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. 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. 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. 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.