Journal article

Pharmacogenetic Study on Risperidone Long-Acting Injection Influence of Cytochrome P450 2D6 and Pregnane X Receptor on Risperidone Exposure and Drug-Induced Side-Effects

Eva Choong, Andrea Polari, Rigobert Hervais Kamdem, Nicola Gervasoni, Caesar Spisla, Eveline Jaquenoud Sirot, Graziella Giacometti Bickel, Guido Bondolfi, Philippe Conus, Chin B Eap

JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY | LIPPINCOTT WILLIAMS & WILKINS | Published : 2013

Abstract

Risperidone is metabolized by polymorphic enzymes, and a large variability in plasma concentration and therapeutic response is observed. Risperidone long-acting injection (RLAI) avoids the first-pass effect, and little is known about the influence of gene polymorphisms involved in its pharmacokinetics. The influence on plasma concentrations of risperidone (RIS), its metabolite 9-hydroxy-risperidone, and on adverse effects were investigated for polymorphisms of cytochrome P450 2D6 (CYP2D6) (*3, *4, *5, *6), CYP3A (CYP3A4*1B, CYP3A4 rs4646437, CYP3A5*3, CYP3A7*1C), ABCB1 (1236C>T, 2677G>T, 3435C>T), NR1/2 coding for pregnane X receptor (rs1523130, rs2472677, rs7643645), and for CYP3A activity ..

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Grants

Awarded by Swiss National Research Foundation


Funding Acknowledgements

This work has been funded in part by the Swiss National Research Foundation (no. 320030-120686) and by a nonrestricted educational grant by Janssen-Cilag Switzerland. The funding sources had no role in the writing of the manuscript or in the decision to submit it for publication.Dr Bondolfi is a consultant of Pfizer, received grants from Janssen-Cilag, and received speaker fees paid for by many different pharmaceutical societies, medical societies, hospitals, and congress organizations. Dr Conus received a nonrestricted educational grant from Bristol-Myers Squibb and Janssen-Cilag and supports for attending conferences from Eli Lilly and Bristol-Myers Squibb. Dr Eap received nonrestricted educational grants from Janssen-Cilag and Bristol-Myers Squibb. He received honoraria for conferences or teaching CME courses from AstraZeneca, Bristol-Myers Squibb, Eli Lily, Essex Chemie, GlaxoSmithKline, Janssen-Cilag, Lundbeck, Novo Nordisk, and Organon. Ms Jaquenoud Sirot was in the advisory board of Janssen-Cilag and received speaker fees paid for by many different pharmaceutical societies, medical societies, hospitals, and congress organizations. The other authors declare no conflicts of interest.