Effects of Cigarette Smoking and Cytochrome P450 2D6 Genotype onFluvoxamine Concentration in Plasma of Japanese Patients

摘要

Fluvoxamine is a selective serotonin reuptake inhibitor widely used in the treatment of depression and otherpsychiatric diseases. The aim of this study was to assess the clinical impact of cigarette smoking on plasmafluvoxamine concentration in Japanese patients, and evaluate whether the cytochrome P450 (CYP) 1A2 andCYP2D6 genotypes have effects on that concentration. Thirty-two Japanese patients receiving fluvoxamine wereenrolled. They were maintained on the same daily dose of fluvoxamine (mean±S.D., 109.4±66.2 mg/d) for atleast 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±6.5 ng/ml/dose) was significantly lower than thatin non-smoker patients (n=26, 22.8±11.2 ng/ml/dose). There was no significant difference for the C/D ratio offluvoxamine in patients with CYP1A2 —3860G/G, —3860G1A, and —3860A1A between non-smokers and smok-ers. Among non-smoker patients, the C/D ratios of fluvoxamine in those with one and two mutated alleles ofCYP2D6 were 1.6- and 1.4-fold higher, respectively, than those with no mutated alleles, though the differencesamong those three genotype groups were not significant. Furthermore, stepwise multiple regression analysis re-vealed that cigarette smoking and daily dose had significant positive correlations with the plasma concentrationof fluvoxamine. Our findings suggest that cigarette smoking has a significant impact on the steady-state plasmaconcentration of fluvoxamine in Japanese patients.