title: Effects of cigarette smoking and cytochrome P450 2D6 genotype on fluvoxamine concentration in plasma of Japanese patients.
abstract: Fluvoxamine is a selective serotonin reuptake inhibitor widely used in the treatment of depression and other psychiatric diseases. The aim of this study was to assess the clinical impact of cigarette smoking on plasma fluvoxamine concentration in Japanese patients, and evaluate whether the cytochrome P450 (CYP) 1A2 and CYP2D6 genotypes have effects on that concentration. Thirty-two Japanese patients receiving fluvoxamine were enrolled. They were maintained on the same daily dose of fluvoxamine (mean + or - S.D., 109.4 + or - 66.2 mg/d) for at least 4 weeks to obtain the steady-state plasma concentration. The steady-state plasma concentration-to-dose (C/D) ratio of fluvoxamine in patients who smoked (n = 6, 11.8 + or - 6.5 ng/ml/dose) was significantly lower than that in non-smoker patients (n = 26, 22.8 + or - 11.2 ng/ml/dose). There was no significant difference for the C/D ratio of fluvoxamine in patients with CYP1A2 -3860G/G, -3860G/A, and -3860A/A between non-smokers and smokers. Among non-smoker patients, the C/D ratios of fluvoxamine in those with one and two mutated alleles of CYP2D6 were 1.6- and 1.4-fold higher, respectively, than those with no mutated alleles, though the differences among those three genotype groups were not significant. Furthermore, stepwise multiple regression analysis revealed that cigarette smoking and daily dose had significant positive correlations with the plasma concentration of fluvoxamine. Our findings suggest that cigarette smoking has a significant impact on the steady-state plasma concentration of fluvoxamine in Japanese patients.
authors.affiliation: Department of Pharmacy Practice and Science, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan. y-kato@u-shizuoka-ken.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Katoh
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchida
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kawai
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Takei
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Namiki
authors.forename: Hisakuni
authors.initials: H
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000097:blood / Q000235:genetics*; D005260:Female; D016666:Fluvoxamine / Q000097:blood*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000097:blood* / Q000235:genetics*; D055815:Young Adult
chemical_list: D019389:Cytochrome P-450 CYP2D6; D016666:Fluvoxamine