Naoki Fukui, Yutaro Suzuki, Kazushi Sawamura, Takuro Sugai, Junzo Watanabe, Yoshimasa Inoue, Toshiyuki Someya
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Therapeutic drug monitoring 2007 AprThis study investigated effects of the 3435 C>T genotype of the adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1, MDR1) gene on the steady-state plasma concentration of fluvoxamine (FLV). Sixty-two psychiatric patients were treated with different doses (50, 100, 150, and 200 mg/d) of FLV. Blood samples were collected after at least 2 weeks of treatment with the same daily dose to obtain steady-state concentrations of FLV, and 3435 C>T genotype was determined by polymerase chain reaction. FLV concentration-to-dose ratio was significantly different among 3435 C>T genotype groups at the 200 mg/d dose (P = 0.019). A post-hoc analysis revealed that FLV concentration-to-dose ratio was significantly higher in the TT genotype group as compared with the CC genotype group at the 200 mg/d dose (median value of concentration-to-dose ratio (ng/mL)/(mg/d), 0.861 vs 0.434, P = 0.026). FLV concentration-to-dose ratio was significantly higher in the CT + TT genotype group than the CC genotype group at the 200 mg/d dose (median value of concentration-to-dose ratio (ng/mL)/(mg/d), 0.618 vs 0.434, P = 0.031). At 50, 100, and 150 mg/d dose, FLV concentration-to-dose ratios were not significantly different among 3435 C>T genotype groups. At 50, 100, and 150 mg/d dose, no significant differences were found in FLV concentration-to-dose ratios between the CT + TT genotype group and CC genotype group. This study suggests that pharmacokinetics of FLV depend on ABCB1 gene polymorphism only at the 200 mg/d dose.
Naoki Fukui, Yutaro Suzuki, Kazushi Sawamura, Takuro Sugai, Junzo Watanabe, Yoshimasa Inoue, Toshiyuki Someya. Dose-dependent effects of the 3435 C>T genotype of ABCB1 gene on the steady-state plasma concentration of fluvoxamine in psychiatric patients. Therapeutic drug monitoring. 2007 Apr;29(2):185-9
PMID: 17417072
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