Dose-dependent effects of the 3435 C>T genotype of ABCB1 gene on the steady-state plasma concentration of fluvoxamine in psychiatric patients.
This 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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
This study suggests that pharmacokinetics of FLV depend on ABCB1 gene polymorphism only at the 200 mg/d dose.
Fukui
Naoki
N
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Suzuki
Yutaro
Y
Sawamura
Kazushi
K
Sugai
Takuro
T
Watanabe
Junzo
J
Inoue
Yoshimasa
Y
Someya
Toshiyuki
T
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D016666:Fluvoxamine / Q000097:blood* / Q000627:therapeutic use; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy*; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000627:therapeutic use
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016666:Fluvoxamine; D027361:Organic Anion Transporters; D017367:Selective Serotonin Reuptake Inhibitors; C513055:ABCB1 protein, human