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

Abstract

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

CLC Number:

R969

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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