MTHFR和MTR的基因多态性对马来酸依那普利叶酸片药动学影响的研究

Effects of Genetic Polymorphism of MTHFR and MTR on the Pharmacokinetics of Enalapril Maleate Folic Acid Tablets

目的:考察亚甲基四氢叶酸还原酶(MTHFR)和蛋氨酸合成酶(MTR)的基因多态性对中国健康成年人口服马来酸依那普利叶酸片后依那普利药动学的影响。方法:36名健康志愿者单剂量口服10mg/0.8mg马来酸依那普利叶酸片后,于不同时间点取血,采用液-质联用法测定血药浓度,并进行血样基因型分析及同型半胱氨酸水平测定。结果:MTHFR存在CC、CT和TT3种基因型,其多态性对依那普利的主要药动学参数未见显著影响;而MTR存在AA、AG2种类型,与AA型相比,AG型对依那普利吸收很好,但排泄较慢。结论:MTHFR基因多态性不影响所研究人群的依那普利药动学,而MTR的AA和AG基因型引起依那普利药动学的差异。

OBJECTIVE： To study the effects of genetic polymorphisms of MTHFR and MTR on the pharmacokinetics of enalapril maleate in Chinese healthy volunteers after administration of Enalapril maleate folic acid tablets. METHODS： Single oral-dose of Enalapril maleate folic acid tablets 10 mg/0.8 mg was given to 36 healthy volunteers. Blood samples were collected at different time points. The plasma concentration of enalapril maleate was determined by LC-MS. The polymorphic alleles of MTHFR and MTR were determined as well as the level of homocysteine in each subject. RESULTS： There were three genotypes of CC, CT and TT in the polymorphic alleles of MTHFR. And no difference was found in main pharmacokinetic parameters of enalapril maleate among three genotypes. There were two genotypes of AA and AG in the polymorphic alleles of MTR, and enalapril maleate absorption of AG genotype group was significantly greater than AA genotype group. CONCLUSION： The genetic polymorphism of MTHFR hasn＇t influenced the pharmacokinetics of enalapril maleate. The AA and AG genotype of MTR may be responsible in individual variability of enalapril maleate pharmacokinetics.