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Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia

The Pharmacogenomics Journal volume 14, pages 452–456 (2014)Cite this article

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Abstract

Risperidone (RIS) is a frequently used efficacious psychotropic drug. However, it prolongs the QTc interval and may cause fatal arrhythmia. Little is known on the determinants of this RIS side effect. RIS is metabolized by CYP2D6, and is subject to drug efflux by P-glycoprotein (P-gp) encoded by the ATP-binding cassette subfamily B member 1 (ABCB1) gene. P-gp removes both RIS and its metabolite 9-OH-RIS from cardiac tissue. To investigate the effect of RIS metabolism and ABCB1 gene polymorphisms on QTc, steady-state plasma RIS and 9-OH-RIS levels, and QTc were measured. CYP2D6, ABCB1 C3435T and G2677T/A genotypes were determined in 66 schizophrenia patients on RIS. QTc was significantly longer in patients with ABCB1 3435CT+3435 TT than in those with 3435CC (P=0.006). ABCB1 G2677T/A genotype did not affect QTc. Multiple regression analysis showed that C/T or T/T genotypes at the ABCB1 C3435T locus, lower weight, and older age prolonged QTc. In summary, the T allele of the ABCB1 C3435T genotype should be considered in future diagnostic development efforts for RIS-associated QT.

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Acknowledgements

We would like to express our gratitude to the study participants. We thank Hiroshi Kusano and Nanako Yamazaki for their excellent technical assistance. This study was funded by a Grant-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Research (# 20591362) to Y Suzuki, and by Mitsubishi Pharma Research Foundation and Health and Labour Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health, H17-kokoro-002) to T Someya.

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Authors and Affiliations

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

    Y Suzuki, N Tsuneyama, N Fukui, T Sugai, J Watanabe, S Ono, M Saito & T Someya

  2. MP-Technopharma Corporation Technology Department, Fukuoka, Japan

    Y Inoue

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  1. Y Suzuki
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Correspondence to Y Suzuki.

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Competing interests

TS has received research support and honoraria from Asahi Kasei, Astellas Pharma, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical, Pfizer Japan, Shionogi, Takeda Pharmaceutical and Yoshitomiyakuhin. The remaining authors declare no conflict of interest.

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The funding sources had no role in the study design; collection, analysis or interpretation of data; writing of the report; or decision to submit the paper for publication.

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Suzuki, Y., Tsuneyama, N., Fukui, N. et al. Effect of risperidone metabolism and P-glycoprotein gene polymorphism on QT interval in patients with schizophrenia. Pharmacogenomics J 14, 452–456 (2014). https://doi.org/10.1038/tpj.2014.6

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