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

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (8): 909-912.

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

杜淑娴, 刘玉清, 田蕾, 刘红, 谢爽, 蒋娟娟, 王平, 华丛笑, 李一石

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

收稿日期:2007-12-13 修回日期:2008-05-26 出版日期:2008-08-26 发布日期:2020-10-12
通讯作者: 刘玉清, 女, 教授, 硕士生导师, 主要从事心血管药物基因组学临床研究。Tel:010-88398395　E-mail:yuqingliu@yahoo.com
作者简介:杜淑娴, 女, 硕士, 主管药师, 主要从事心血管药物临床研究。Tel:010-88396298　E-mail:dsxian2006@126.com

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

DU Shu-xian, LIU Yu-qing, TIAN Lei, LIU Hong, XIE Shuang, JlANG Juan-juan, WANG Ping, HUA Cong-xiao, LI Yi-shi

Key Laboratory of Clinical Trial Research in Cardiovascular Drugs Ministry of Health, FuwaICardiovascular Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing 100037, China

Received:2007-12-13 Revised:2008-05-26 Online:2008-08-26 Published:2020-10-12

摘要/Abstract

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-MN 60 mg, 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t_max差异没有统计学意义;尽管G/G基因型与g a基因型相比, C_max和AUC_0-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。

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

Abstract: AIM:To investigate the effects of polymorphisms of aldehyde dehydrogenase 2 gene(ALDH2)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 pharmacokinetics.RESULTS:In these 22 volunteers, 13 homozygous Gg and 9 heterozygous GA genotypes for ALDH2 at positions of Glu504Lys were detected by PCRRFLP.IS-5-MN plasma concentration, AUC_0-t, Cmax and t_max 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.

Key words: isosorbide-5-mononitrate, aldehyde dehydrogenase 2, genetic polymorphism, pharmacokinetics

中图分类号:

R969

杜淑娴, 刘玉清, 田蕾, 刘红, 谢爽, 蒋娟娟, 王平, 华丛笑, 李一石. 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[J]. 中国临床药理学与治疗学, 2008, 13(8): 909-912.

DU Shu-xian, LIU Yu-qing, TIAN Lei, LIU Hong, XIE Shuang, JlANG Juan-juan, WANG Ping, HUA Cong-xiao, LI Yi-shi. Effects of polymorphisms of aldehyde dehydrogenase 2 gene on pharmacokinetic characteristics of isosorbide-5-mononitrate extended action tablet in Chinese healthy subjects[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(8): 909-912.

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