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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。
OBJECTIVE: To investigate the pharmacokinetics of oral ALDH2 Glu504Lys (G504A) polymorphism of isoform 5-isononitrate mononitrate (IS-5-MN) in Chinese healthy volunteers influences. METHODS: Subjects were screened in 45 patients. Subjects received single oral IS-5-MN60mg and blood samples were collected at different time points within 36 hours after drug administration. The drug concentrations of IS-5-MN were determined by HPLC-MS. ALDH2 was genotyped by PCR-RFLP and the effects of different genotypes on the pharmacokinetics of IS-5-MN were analyzed. RESULTS: Twenty-two subjects were screened out of 45 patients, including 13 wild-type homozygotes and 9 heterozygotes. There was no significant difference in plasma concentrations of t-1 and IS-5-MN between the two genotypes, although Cmax and AUC0-t were increased by 12.4% and 15.3%, respectively, in G / G genotype compared with G / A genotype , But the differences were not statistically significant. CONCLUSION: The preliminary observation did not find ALDH2 gene polymorphism and IS-5-MN pharmacokinetics.