Effects of CYP2D6 genotypes on plasma concentrations of risperidone and enantiomers of 9-hydroxyrisperidone in Japanese patients with schizophrenia.
作者： Norio Yasui-Furukori , Kazuo Mihara , Tsuyoshi Kondo , Takahiro Kubota , Tatsuji Iga
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摘要: It has been shown that risperidone (+)-9-hydroxylation is enantioselectively catalyzed by the polymorphic CYP2D6 in human liver. This study aimed to examine effect of genotype on schizophrenic patients. Subjects were 38 Japanese inpatients receiving 6 mg/day risperidone. Plasma concentrations and (+)- (-)-9-hydroxyrisperidone at steady state quantified using LC/MS/MS HPLC with alpha 1 acid-AGP chiral column, respectively. The CYP2D6*5(*5) *10 alleles identified polymerase chain reaction (PCR) methods. Twenty patients had no mutated allele, 14 one 4 two alleles. There significant differences steady-state plasma (ANOVA; p < 0.0001) among three groups, while did not affect (+)-9-hydroxyrisperidone (p = 0.314) or 0.957). concentration ratio 9-hydroxyrisperidone was strongly dependent genotypes. suggests activity influences risperidone/9-hydroxyrisperidone ratios but unlikely determine enantio-selectivity clinical situation.
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