| Objective This study was to investigate the correlation between CYP2D6*10, CYP3A5*3, MDR1C3435T, G2677T, C1236T genetic polymorphisms and steady-state plasma concentration of risperidone and9-hydroxyrisperidone in Chinese schizophrenic patients treated with risperidone. Methods:The genetypes of CYP3A5*3, MDR1C3435T, G2677T and C1236T were performed by the polymerase chain reaction-ligation detection reaction (PCR-LDR). DNA sequencing were carried out to detect genetype of CYP2D6*10. The steady-state plasma concentrations of risperidone and9-hydroxyrisperidone were determined by high performance liquid chromatograpy-tandem mass spectrometry (LC-MS/MS). The dose-corrected plasma concentrations (C/D) of risperidone,9-hydroxyrisperidone and active moiety (risperidone plus9-hydroxyrisperidone) as dependent variable. Multiple linear regression analyses were used to detect association between C/D of risperidone,9-hydroxyrisperidone and active moiety and several factors including CYP2D6*10, CYP3A5*3and MDR1(C3435T, G2677T and C1236T) genetypes. Results:Seventy-eight Chinese schizophrenic patients were enrolled. The results demonstrated that CYP2D6*10(Beta=0.495, P<0.001) and CYP3A5*3genotypes (Beta=0.225, P<0.05) correlated with the C/D of risperidone; CYP3A5*3genotypes (Beta=0.257, P<0.05) correlated with C/D of9-hydroxyrisperidone; CYP2D6*10(Beta=0.271, P<0.05)and CYP3A5*3genotypes (Beta=0.272, P<0.05) correlated with the C/D of active moiety. No correlations were found between C/D of risperidone,9-hydroxyrisperidone and active moiety and MDR1C3435T, G2677T and C1236T genotypes. Conclusions:This finding suggest that CYP2D6*10and CYP3A5*3genetypes may play an important role in the steady-state plasma concentration of risperidone and9-hydroxyrisperidone in han Chinese schizophrenic patients. Application of CYP2D6*10and CYP3A5*3genetype to clinical individualized medication of risperidone in han Chinese schizophrenic patients. |
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