title: Impact of the ABCB1 gene polymorphism on plasma 9-hydroxyrisperidone and active moiety levels in Japanese patients with schizophrenia.
abstract: 9-Hydroxyrisperidone (9-OH-RIS) is an active metabolite of the antipsychotic drug risperidone (RIS). The total active moiety level, in other words the sum of the RIS and 9-OH-RIS serum levels, may be important for estimating the clinical effects of RIS treatment. However, there have been no consistent results reported regarding the relationship between cytochrome P450 (CYP) 2D6 or adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) variant alleles and 9-OH-RIS or total active moiety plasma levels. Seventy-four Japanese patients treated with RIS were examined in the present study. Steady-state plasma RIS and 9-OH-RIS were measured. The CYP2D6*5, CYP2D6*10, ABCB1 3435C>T, and ABCB1 2677G>T/A genotypes were detected. Multiple regression analysis showed that the dose-corrected plasma RIS levels were significantly correlated with the number of CYP2D6 variant alleles and ABCB1 3435C>T genotypes, whereas the 9-OH-RIS and total active moiety levels were significantly correlated with the ABCB1 3435C>T genotypes and with age. On the other hand, the ABCB1 2677G>T/A genotypes did not affect plasma RIS, 9-OH-RIS, or total active moiety levels. The ABCB1 3435C>T genetic polymorphism may predict plasma 9-OH-RIS and total active moiety levels.
authors.affiliation: Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Nobuto
authors.initials: N
authors.lastname: Tsuneyama
authors.forename: Naoki
authors.initials: N
authors.lastname: Fukui
authors.forename: Takuro
authors.initials: T
authors.lastname: Sugai
authors.forename: Junzo
authors.initials: J
authors.lastname: Watanabe
authors.forename: Shin
authors.initials: S
authors.lastname: Ono
authors.forename: Mami
authors.initials: M
authors.lastname: Saito
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007555:Isoxazoles / Q000493:pharmacokinetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011110:Polymorphism, Genetic; D011743:Pyrimidines / Q000493:pharmacokinetics*; D012044:Regression Analysis; D018967:Risperidone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D014150:Antipsychotic Agents; D007555:Isoxazoles; D011743:Pyrimidines; D019389:Cytochrome P-450 CYP2D6; D018967:Risperidone; D000068882:Paliperidone Palmitate