OBJECTIVE: To discuss the correlation between multidrug resistance gene (MDR1) polymorphisms and plasma concentration of risperidone, 9-hydroxyrisperidone and total active substance in Han patients with schizophrenia. METHODS: 78 Han inpatients with schizophrenia in Mental Health Institute of Second Xiangya Hospital of Central South University from Dec. 2011 to Jan. 2013 were selected, LC-MS/MS was conducted to determine the plasma concentration of risperidone, 9-hydroxyrisperidone and total active substance, PCR-LDR was adopted to determine the genotyping of C1236T, G2677T and C3435T of patients, and one-way ANOVA was used to detect the correlation between C1236T, G2677T and C3435T polymorphisms and plasma concentration/dose calibration ratio (C/D) value of risperidone, 9-hydroxyrisperidone and total active substance. RESULTS: The average plasma concentrations of risperidone, 9-hydroxyrisperidone and total active substance for 78 patients were (13.58±8.31), (25.62±15.52) and (39.24±25.76) ng/ml, respectively; the distribution frequencies of C1236T, G2677T and C3435T met the Hardy-Weinberg equilibrium (P>0.05); the risperidone C/D value of patients with C12367T CT and TT genotype were higher than those with CC genotype, risperidone and total active substance C/D values of patients with G2677T TT genotype were higher than those with GG genotype, the differences were statistically significant (P<0.05); while there were no significant differences in analyte C/D values in other patients (P>0.05). CONCLUSIONS: The MDR1 C1236T and G2677T polymorphisms are associated with plasma concentration of risperidone and total active substance in Han patients with schizophrenia.
关键词
多药耐药基因多态性利培酮9-羟基利培酮总活性物血药浓度/剂量校正比相关性
Keywords
Multidrug resistanceGene polymorphismRisperidone9-hydroxyrisperidoneTotal active substancePlasma concentration/dose calibration ratioCorrelation