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Impact of the ABCB1 Gene Polymorphism on Plasma 9-Hydroxyrisperidone and Active Moiety Levels in Japanese Patients With Schizophrenia

Suzuki, Yutaro MD, PhD; Tsuneyama, Nobuto MD; Fukui, Naoki MD, PhD; Sugai, Takuro MD, PhD; Watanabe, Junzo MD, PhD; Ono, Shin MD, PhD; Saito, Mami MD; Someya, Toshiyuki MD, PhD

Journal of Clinical Psychopharmacology: June 2013 - Volume 33 - Issue 3 - p 411–414
doi: 10.1097/JCP.0b013e31828ecd52
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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.

From the Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Received November 11, 2011; accepted after revision August 17, 2012.

Reprints: Toshiyuki Someya, MD, PhD, Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, 757 Asahimachidori-ichibancho, Chuo-ku, Niigata 951-8510, Japan (e-mail: psy@med.niigata-u.ac.jp).

This study was supported by a research grant (H17-kokoro-002) from the Psychiatric and Neurological Diseases and Mental Health of the Ministry of Health, Labour and Welfare; and research grants (17A-1 and 20B-1) from the Nervous and Mental Disorders of the Ministry of Health, Labour and Welfare.

© 2013 Lippincott Williams & Wilkins, Inc.