健康人乙醛脱氢酶2基因型对5-单硝酸异山梨醇酯缓释片药代动力学影响的研究  

Effects of polymorphisms of aldehyde dehydrogenase 2 gene on pharmacokinetic characteristics of isosorbide-5-mononitrate extended action tablet in Chinese healthy subjects

作　　者：杜淑娴[1] 刘玉清[1] 田蕾[1] 刘红[1] 谢爽[1] 蒋娟娟[1] 王平[1] 华丛笑[1] 李一石[1] 

机构地区：[1]北京协和医学院中国医学科学院北京阜外心血管病医院卫生部心血管药物临床研究重点实验室,北京100037

出　　处：《中国临床药理学与治疗学》2008年第8期909-912,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:探讨乙醛脱氢酶2基因(ALDH2)Glu504Lys(G504A)多态性对中国健康受试者口服5-单硝酸异山梨醇酯缓释片(IS-5-MN)药代动力学的影响。方法:在45例人群中筛选受试者,受试者单次口服IS-5-MN60mg,采集服药后36h内不同时间点的血样,HPLC-MS测定IS-5-MN的药物浓度。利用PCR-RFLP方法对ALDH2进行基因分型,分析不同基因型对IS-5-MN药代动力学的影响。结果:在45例人群中筛选出22名受试者,其中野生型纯合子13例,杂合子9例。两组基因型的IS-5-MN血药浓度和tmax差异没有统计学意义;尽管G/G基因型与G/A基因型相比,Cmax和AUC0-t分别升高了12.4%和15.3%,但差异均无统计学意义。结论:初步观察未发现ALDH2基因多态性与IS-5-MN的药代动力学有关。AIM： To investigate the effects of polymorphisms of aldehyde dehydrogenase 2 gene（ AL- DH2） at positions Glu504Lys on pharmacokinetic （PK） characteristics of isosorbide-5-mononitrate （IS-5-MN） in Chinese healthy volunteers. METHODS：Among 45 persons, twenty-two healthy male volunteers were selected and orally taken 60 mg IS-5-MN. An HPLC-MS method was applied to analyze IS-5-MN plasma concentration. ALDH2 genotype was determined by PCRRFLP. Pharmacokinetic analysis was performed to assess the effects of the genotype on IS-5-MN phannacokinetics. RESULTS： In these 22 volunteers, 13 homozygous GG and 9 heterozygous GA genotypes for AL-DH2 at positions of Glu504Lys were detected by PCR- RFLP. IS-5-MN plasma concentration, AUC0-t, Cmax and tmax did not show significant statistical difference （ P 〉 0.05） in the two groups. CONCLUSION： The polymorphisms of ALDH2 gene at positions of Glu504Lys could not influence the pharmacokinetics of IS-5-MN in the research.

关 键 词：5-单硝酸异山梨醇酯缓释片 乙醛脱氢酶2 基因多态性 药代动力学 

分 类 号：R969[医药卫生—药理学]