title: 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.
authors.affiliation: Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Watanabe
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Naoki
authors.initials: N
authors.lastname: Fukui
authors.forename: Takuro
authors.initials: T
authors.lastname: Sugai
authors.forename: Shin
authors.initials: S
authors.lastname: Ono
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Inoue
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
mesh_terms: D000328:Adult; D000368:Aged; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016666:Fluvoxamine / Q000097:blood* / Q000493:pharmacokinetics*; D018628:Gene Dosage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D019389:Cytochrome P-450 CYP2D6; D016666:Fluvoxamine; D017367:Selective Serotonin Reuptake Inhibitors