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

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概要

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• 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.

• 日本薬学会の論文

著者

• KAGAWA Yoshiyuki

  Department of Pharmacy, Mie University Hospital, Faculty of Medicine, Mie University

• KAWAKAMI Junichi

  Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, University of Tokyo

• YAMADA Shizuo

  Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence (COE) Program, S

• UCHIDA Shinya

  Department of Pharmacokinetics and Pharmacodynamics and Global COE Program, School of Pharmaceutical

• Uchida Shinya

  Department Of Pharmacokinetics And Pharmacodynamics School Of Pharmaceutical Sciences University Of

• Uchida Shinya

  Department Of Biopharmacy School Of Pharmaceutical Sciences University Of Shizuoka

• NAMIKI Noriyuki

  Department of Pharmacy, The Jikei University School of Medicine Daisan Hospital

• Namiki Noriyuki

  Department Of Earth And Planetary Sciences Kyushu University

• MORI Norio

  Department of Psychiatry, Hamamatsu University School of Medicine

• KAWAI Masayoshi

  Department of Psychiatry and Neurology, Hamamatsu University School of Medicine

• Kagawa Yoshiyuki

  Department Of Clinical Pharmaceutics And Pharmacy Practice Faculty Of Pharmaceutical Sciences Univer

• Katoh Yasuhiro

  Department of Pharmacy Practice and Science, School of Pharmaceutical Sciences, University of Shizuo

• Takei Noriyoshi

  Department of Psychiatry, Hamamatsu University School of Medicine

• Hashimoto Hisakuni

  Nihon Pharmaceutical University

• Yamada Shizuo

  Department Of Biophamacy School Of Pharmaceutical Sciences University Of Shizuoka

• Katoh Yasuhiro

  Department Of Orthopaedic Surgery Nagoya City University Medical School

• Mori Norio

  Department Of Neuropsychiatry Fukushima Medical College

• Kawakami Junichi

  Department Of Hospital Pharmacy Hamamatsu University School Of Medicine

• Katoh Yasuhiro

  Departments Of Pharmacy Practice & Science School Of Pharmaceutical Sciences University Of Shizu

• Kawai Masayoshi

  Department Of Mechanical Engineering Ibaraki University

• Uchida Shinya

  Department Of Anesthesiology Gunma University Hospital

• Yamada Shizuo

  Department of Pharmacokinetics & Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka

• Uchida Shinya

  Department of Pharmacy Practice and Science, University of Shizuoka

• Katoh Yasuhiro

  Department of Pharmacy Practice and Science, University of Shizuoka

• Kagawa Yoshiyuki

  Department of Clinical Pharmaceutics & Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka

• Namiki Noriyuki

  Department of Pharmacy Practice and Science, University of Shizuoka

• Namiki Noriyuki

  Department of Clinical Pharmacology & Therapeutics, Hamamatsu University School of Medicine

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