摘要
目的:探讨汉族抑郁症患者CYP2D6基因多态性对文拉法辛体内代谢的影响。方法:以79名抑郁症住院患者为研究对象,采用液相色谱-质谱/质谱联用技术测定患者体内文拉法辛及去甲文拉法辛血药浓度,采用sanger测序对患者CYP2D6*4基因(rs3892097)、CYP2D6*5基因(基因缺失)、CYP2D6*10基因(rs1065852)和CYP2D6*14基因(rs5030865)进行SNPs分型。结果:(1)CYP2D6*4、CYP2D6*5、CYP2D6*14 3个基因的突变检出率为0%。根据CYP2D6*10(rs1065852)基因分型结果将患者分为3组:CC组(15例,19.0%)、CT组(25例,31.6%)和TT组(39例,49.4%),其中T等位基因突变频率为65.2%;(2)3组间C_(VEN)、C_(ODV)、剂量校正前后C_(VEN)+C_(ODV)浓度差异无统计学意义;CC、CT和TT组C_(ODV)/C_(VEN)分别为6.0、4.0和3.0,其中CC与TT组间差异有高度统计意义(P<0.01),CC与CT组间差异有统计意义(P<0.05)。(3)不同性别组间C_(ODV)和剂量校正前后的C_(VEN)+C_(ODV)差异有统计意义:女性组C_(ODV)(368.6 ng·mL^(-1))高出男性组(267.0 ng·mL^(-1))38.1%;女性组C_(VEN)+C_(ODV)(499.3 ng·mL^(-1))高出男性组(406.7 ng·mL^(-1))22.8%;女性组剂量校正后C_(VEN)+C_(ODV)(2.5 ng·mL^(-1)·mg^(-1))高出男性组(2.1 ng·mL^(-1)·mg^(-1))19.0%。结论:研究未发现不同CYP2D6基因型组间药物浓度差异有统计意义,但不同基因型组间文拉法辛代谢率(C_(ODV)/C_(VEN))差异有显著性。文拉法辛体内代谢存在性别差异,但临床疗效是否有差异有待进一步研究;相对于男性患者,女性患者暴露于更高的药物浓度之下,发生药物不良反应的风险更高,因此临床治疗女性患者时剂量调整需更加缓慢和谨慎。
OBJECTIVE To investigate the effect of CYP2 D6 gene polymorphism on venlafaxine metabolism in Chinese Han patients with depression. METHODS Plasma concentration of Venlafaxine and O-desmethylvenlafaxine was determined with liquid chromatography-mass spectrometry/mass spectrometry and the genotype of CYP2 D6 * 4(rs3892097), CYP2 D6 * 5 genes(gene deletion), CYP2 D6 * 10 genes(rs1065852) and CYP2 D6 * 14(rs5030865) were analysed with sanger sequencing in 79 inpatients with depression. RESULTS(1)The mutation detection rate of CYP2 D6* 4, CYP2 D6* 5 and CYP2 D6*14 was 0%. According to the genotyping of CYP2 D6*10(rs1065852), the patients were divided into three groups: CC group(15, 19.0%), CT group(25,31.6%)and TT group(39, 49.4%), in which the frequency of T allele mutation was 65.2%.(2)No significant difference was observed between three groups in CVEN, CODV, CVEN+CODV and dose-adjusted CVEN+CODV. CODV/CVEN in CC, TT and CT group respectively was 6.0, 4.0 and 3.0,in which the difference between CC and TT groups was highly statistically significant(P < 0.01) and a statistically significant difference was observed between CC and CT group(P < 0.05). 3 There was a statistically significant difference between CODV,CVEN+CODV and dose-adjusted CVEN+CODV in different gender groups: CODV of female patients(368.6 ng·mL-1)was 38.1% higher than that of male patients(267.0 ng·mL-1);CVEN+CODV of female patients(499.3 ng·mL-1) was 22.8% higher than that of male patients(406.7 ng·mL-1).Dose-adjusted CVEN+CODV of female patients(2.5 ng·mL-1·mg-1) was 19.0% higher than that of male patients(2.1 ng·mL-1·mg-1).CONCLUSION No significant difference was observed in drug concentrations between different CYP2 D6 genotype groups, but there was a statistically significant difference in venlafaxine metabolic rate(CODV/CVEN) between different genotype groups. There is a gender difference in the metabolism of venlafaxine in vivo, but whether there is a difference in clinical efficacy remains to be further studied;compared to male patients, female patients are exposed to higher drug concentrations and have a higher risk of adverse drug reactions. Therefore, dose adjustments need to be made more slowly and cautiously when treating female patients.
作者
韦龙静
陈瑜
耿纪婷
王强
姚志剑
WEI Long-jing;Chen Yu;Gen Ji-ting;Wang Qiang;Yao Zhi-jian(Department of Pharmacy,Nanjing Brain Hospital Affiliated to Nanjing Medical University,Jiangsu Nanjing 210029,China;Department of Psychiatry,Nanjing Brain Hospital Affiliated to Nanjing Medical University,Jiangsu Nanjing 210029,China;Nanjing Medical University,Jiangsu Nanjing 210029,China;Medical School,Nanjing University,Jiangsu Nanjing 210029,China)
出处
《中国医院药学杂志》
CAS
北大核心
2019年第5期497-501,共5页
Chinese Journal of Hospital Pharmacy
基金
江苏省临床医学科技专项(编号:BL2014009)
