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标题：Effects of Cigarette Smoking and Cytochrome P450 2D6 Genotype on Fluvoxamine Concentration in Plasma of Japanese Patients
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作者：Yasuhiro Katoh ; Shinya Uchida ; Masayoshi Kawai 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2010
卷号：33
期号：2
页码：285-288
DOI：10.1248/bpb.33.285
出版社：The Pharmaceutical Society of Japan
摘要：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±S.D., 109.4±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±6.5 ng/ml/dose) was significantly lower than that in non-smoker patients ( n =26, 22.8±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.
关键词：fluvoxamine;cigarette smoking;cytochrome P450 2D6;cytochrome P450 1A2;genetic polymorphism