Impact of the ABCB1 gene polymorphism on plasma 9-hydroxyrisperidone and active moiety levels in Japanese patients with schizophrenia

• Published in: Journal of clinical psychopharmacology Vol. 33; no. 3; p. 411
• Main Authors: Suzuki, Yutaro, Tsuneyama, Nobuto, Fukui, Naoki, Sugai, Takuro, Watanabe, Junzo, Ono, Shin, Saito, Mami, Someya, Toshiyuki
• Format: Journal Article
• Language: English
• Published: United States 01.06.2013
• Subjects: Adult; Age Factors; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - therapeutic use; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Cytochrome P-450 CYP2D6 - genetics; Female; Genotype; Humans; Isoxazoles - pharmacokinetics; Japan; Male; Middle Aged; Paliperidone Palmitate; Polymorphism, Genetic; Pyrimidines - pharmacokinetics; Regression Analysis; Risperidone - pharmacokinetics; Risperidone - therapeutic use; Schizophrenia - drug therapy; Young Adult
• ISSN: 1533-712X
• DOI: 10.1097/JCP.0b013e31828ecd52

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.