BACKGROUND AND PURPOSE: The objective of this study was to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics. EXPERIMENTAL APPROACH: Seventy-two healthy Korean volunteers receiving a single oral dose of 2 mgrisperidone were included in this study. KEY RESULTS: Significant differences were observed between the ABCB1 3435C>T genotypes for the pharmacokinetic parameters (peak serum concentration) of risperidone and the active moiety (risperidone and its main metabolite, 9-hydroxyrisperidone). There were no significant differences in the area under the serum concentration-time curves of risperidone and the active moiety among the ABCB1 2677G>T/A and 3435C>T genotypes. However, the peak serum concentration and area under the serum concentration-time curves were significantly different among the ABCB1 3435C>T genotypes in CYP2D6*10/*10. CONCLUSIONS AND IMPLICATIONS: These findings indicate that polymorphisms of ABCB1 3435C>T in individuals with CYP2D6*10/*10, which has low metabolic activity, could play an important role in the potential adverse effects or toxicity of risperidone.
RCT Entities:
BACKGROUND AND PURPOSE: The objective of this study was to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics. EXPERIMENTAL APPROACH: Seventy-two healthy Korean volunteers receiving a single oral dose of 2 mg risperidone were included in this study. KEY RESULTS: Significant differences were observed between the ABCB1 3435C>T genotypes for the pharmacokinetic parameters (peak serum concentration) of risperidone and the active moiety (risperidone and its main metabolite, 9-hydroxyrisperidone). There were no significant differences in the area under the serum concentration-time curves of risperidone and the active moiety among the ABCB1 2677G>T/A and 3435C>T genotypes. However, the peak serum concentration and area under the serum concentration-time curves were significantly different among the ABCB1 3435C>T genotypes in CYP2D6*10/*10. CONCLUSIONS AND IMPLICATIONS: These findings indicate that polymorphisms of ABCB1 3435C>T in individuals with CYP2D6*10/*10, which has low metabolic activity, could play an important role in the potential adverse effects or toxicity of risperidone.
Authors: Adrián LLerena; Roland Berecz; Pedro Dorado; César Sanz de la Garza; Maria Jesús Norberto; Macarena Cáceres; José Ramón Gutiérrez Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2003-01-05 Impact factor: 3.205
Authors: C Rafaniello; M Sessa; F F Bernardi; M Pozzi; S Cheli; D Cattaneo; S Baldelli; M Molteni; R Bernardini; F Rossi; E Clementi; C Bravaccio; S Radice; A Capuano Journal: Pharmacogenomics J Date: 2017-07-18 Impact factor: 3.550