线粒体乙醛脱氢酶2基因多态性对5-单硝酸异山梨酯缓释片对健康受试者药物代谢的影响

Effects of aldehyde dehydrogenase 2 gene polymorphism on the drug metabolism of isosorbide-5-mononitrate sustained-release tablets in healthy volunteers

目的研究不同线粒体乙醛脱氢酶(ALDH2)基因型对5-单硝酸异山梨酯(IS-5-MN,抗心绞痛药)缓释片药物代谢的影响。方法用PCR-RFLP测定ALDH2基因型后,分为2组,入组22名健康男性受试者。单次口服IS-5-MN60mg,血药浓度测定用HPLC-MS法;同时用脉搏波分析仪测量受试者脉搏波参数值;详细记录受试者的不良反应。结果基因型为ALDH2*1/1和ALDH2*1/2的2组受试者在血药浓度、脉搏波参数、不良反应方面无明显差异;但同组内受试者的脉搏波参数值在服药前后有显著统计学差异(P<0.05)。结论ALDH2基因多态性可能不影响IS-5-MN在健康受试者体内的代谢及药物作用。

Objective To investigate aldehyde dehydrogenase 2（ALDH2） gene polymorphism on the metabolism of isosorbide-5-mononitrate （IS-5-MN） sustained-release tablets in healthy volunteers.Methods Apply PCR-RFLP to measure the genotypes of ALDH2 gene,subjects are divided into two groups according to their genotypes. Twenty-two healthy subjects are selected to take 60 mg IS-5-MN in single does,plasma concentration of IS-5-MN are measured by HPLC-MS in different specific time. Use pulse wave appearance to measure pulse wave analysis （PWA） parameters in blank situation and after taking medicine. Adverse effect was also recorded. Result The parameters of PWA, plasma concentration and adverse effect had no significant differences between the ALDH2 ＊ 1/land ALDH2 ＊ 1/2 genotypes. But the PWA parameters had significant statistic differences in every single group. Conclusion AL- DH2 gene polymorphism perhaps has no significant effect on the IS-5-MN metabolism.