多药耐药基因多态性与利培酮及其代谢物血药浓度的相关性

发布时间：2018-10-25 19:11

【摘要】：目的:探讨我国汉族精神分裂症患者多药耐药基因(MDR1)多态性与利培酮、9-羟基利培酮及总活性物血药浓度的相关性。方法:选择2011年10月-2013年1月中南大学湘雅二医院精神卫生研究所的汉族精神分裂症住院患者78例,采用高效液相色谱-串联质谱法测定其利培酮、9-羟基利培酮和总活性物的血药浓度,采用聚合酶链-连接酶检测反应法检测患者MDR1C1236T、G2677T和C3435T的基因分型,采用单因素方差分析考察MDR1基因多态性与利培酮、9-羟基利培酮及总活性物血药浓度/剂量校正比(C/D)值的相关性。结果:78例患者体内利培酮、9-羟基利培酮及总活性物的平均血药浓度分别为(13.58±8.31)、(25.62±15.52)、(39.24±25.76)ng/ml;C1236T、G2677T和C3435T各基因型分布频率均符合Hardy-Weinberg平衡(P0.05);C1236T CT和TT型患者利培酮的C/D值高于CC型患者,G2677T TT型患者利培酮与总活性物的C/D值均高于GG型患者,差异均有统计学意义(P0.05);而其他基因型患者体内各待测物C/D值间的差异均无统计学意义(P0.05)。结论:汉族精神分裂症患者MDR1 C1236T和G2677T多态性与利培酮及总活性物的血药浓度相关。
[Abstract]:Objective: to investigate the association of multidrug resistance gene (MDR1) polymorphism with risperidone, 9-hydroxyrisperidone and total active drug concentration in Chinese patients with schizophrenia. Methods: from October 2011 to January 2013, 78 inpatients with schizophrenia of Han nationality were selected from the Institute of Mental Health, Xiangya second Hospital, Central South University, and their risperidone was determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The serum concentrations of 9-hydroxyrisperidone and total active compounds were detected by polymerase chain reaction (PCR) and C3435T genotyping, and the polymorphism of MDR1 gene and risperidone were investigated by single factor variance analysis (ANOVA). Correlation of plasma concentration / dose correction ratio (C / D) of 9-hydroxy risperidone and total active substance. Results: the mean serum concentrations of risperidone, 9-hydroxyrisperidone and total active compounds in 78 patients were (13.58 卤8.31), (, 25.62 卤15.52), (, 39.24 卤25.76) ng/ml;, respectively. The genotypes of C1236T G2677T and C3435T all accord with Hardy-Weinberg equilibrium (P0.05). The C / D value of risperidone in C1236T CT and TT type patients was higher than that in CC type patients, and the C / D values of risperidone and total active compounds in G2677T TT patients were significantly higher than those in GG type patients (P0.05). However, there was no significant difference in C / D values among other genotypes (P0.05). Conclusion: the polymorphisms of MDR1 C1236T and G2677T were associated with the plasma concentrations of risperidone and total active compounds in patients with schizophrenia in Han nationality.
【作者单位】：杭州市第一人民医院药学部;中南大学湘雅二医院临床药学研究室;
【分类号】：R749

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