Objective: To investigate the effects of CYP2C9 and CYP2A6 genetic polymorphisms on plasma concentrations of sodium valproate (VPA) in the epileptic children. Methods: Epileptic children treated with sodium valproate only were collected in our study. Fluorescence polarization immunoassay was performed to measure plasma concentrations of sodium valproate. Direct sequencing and nest-PCR were applied to identify the genotypes of CYP2C9 and CYP2A6. One-way ANOVA was performed to analyze the influence of the polymorphisms on plasma concentrations of sodium valproate. Results: Patients were divided into 3 groups according to the genotypes of CYP2C9 and CYP2A6: extensive metabolizers (EM, CYP2C9*1*1 & CYP2A6*1*1), intermediate metabolizers (IM, CYP2C9*1*3 & CYP2A6*1*1 or CYP2C9*1*1 & CYP2A6*1*4), and poor metabolizers (PM, CYP2C9*1*3 & CYP2A6*1*4 or CYP2A6*4*4), and the frequencies of the three groups were 73.5%, 24.1%, and 2.4%, respectively. The standardized blood drug concentration of IM was significantly higher than that of EM (P<0.05). The mean of standardized blood drug concentration of PM was higher than the others, but there were no significant differences between them (P>0.05). Conclusion: The plasma concentrations of sodium valproate can be affected by the polymorphisms of CYP2C9 and CYP2A6. Clinicians can choose appropriate initial dosage by detecting the genotypes.
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Zhu Mingmei, Jing Xia, Sun Fang, Zhan Wen. Effects of CYP2C9 and CYP2A6 genetic polymorphisms on plasma concentrations of sodium valproate[J].,2017,(1):40-43.