Dose-dependent effect of the CYP2D6 genotype on the steady-state fluvoxamine concentration.

Abstract:

:Several studies have reported that the cytochrome P450 (CYP) 2D6 plays an important role in the fluvoxamine metabolism. However, some other studies have reported that the CYP2D6 genotype has no major impact on the fluvoxamine concentration. This study investigated the dose-dependent effect of CYP2D6-variant alleles on the steady-state fluvoxamine concentration. There were 23 patients whose plasma concentrations of fluvoxamine were measured at 4 doses (50, 100, 150, and 200 mg/d). The differences in the plasma fluvoxamine concentration were analyzed between 2 genotype groups divided by the number of CYP2D6-variant alleles (with 0 and 1 or 2 variant alleles). The results demonstrated the nonlinear kinetics of fluvoxamine metabolism, and the degree of nonlinear kinetics decreased as the dose was increased. Significant differences in fluvoxamine concentration were observed between the subjects with 0 variant alleles and the subjects with 1 or 2 variant alleles (P = 0.044) when they were treated by 50 mg of fluvoxamine. There were no significant differences in the plasma concentration of fluvoxamine at 100, 150, and 200 mg/d. The present study suggests that the effect of the CYP2D6 genotype on fluvoxamine metabolism is greater at lower doses of fluvoxamine.

journal_name

Ther Drug Monit

authors

Watanabe J,Suzuki Y,Fukui N,Sugai T,Ono S,Inoue Y,Someya T

doi

10.1097/FTD.0b013e31818d73b3

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

705-8

issue

6

eissn

0163-4356

issn

1536-3694

journal_volume

30

pub_type

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