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Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of risperidone in healthy subjects with CYP2D6 * 10 /* 10
Author(s) -
Yoo HeeDoo,
Lee SangNo,
Kang HyunAh,
Cho HeaYoung,
Lee IlKwon,
Lee YongBok
Publication year - 2011
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2011.01385.x
Subject(s) - risperidone , pharmacokinetics , cyp2d6 , active metabolite , pharmacology , genotype , metabolite , medicine , adverse effect , dopamine antagonist , pharmacogenetics , biology , schizophrenia (object oriented programming) , genetics , psychiatry , haloperidol , gene , dopamine
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.