埃索美拉唑对不同CYP2C19基因型中国人健康志愿者胃内pH的影响(英文)  

Effect of esomeprazole on intragastric pH in healthy Chinese with different CYP2C19 genotypes

作　　者：仲珑瑾[1] 程能能[1] 李兆申[2] 陈斌艳[1] 王永铭[1] 

机构地区：[1]复旦大学药学院药理教研室,上海200032 [2]中国人民解放军第二军医大学长海医院消化内科,上海200433

出　　处：《中国临床药学杂志》2004年第3期129-132,共4页Chinese Journal of Clinical Pharmacy

摘　　要：目的 :研究埃索美拉唑 (Eso)对胃内pH的影响是否与CYP2C19基因型有相关性。方法 :采用PCR RFLP方法对CYP2C19进行基因分型后 ,予Eso 4 0mg ,po ,qd ,连服 5d ,监测第 1,5次给药前 15min及给药后 2 4h胃内pH。结果 :2 7名志愿者分为 3种基因型 :10名纯合子快代谢型 (homEMs) ,14名杂合子快代谢型 (hetEMs)和 3名慢代谢型 (PMs)。在d 1和d 5 ,口服Eso 4 0mg后 2 4h胃内pH中位数平均值各基因型间无统计学差异 ,2 4h中胃内pH >4的时间百分比PMs和EMs之间有统计学差异 ,2 4h胃内pH >4的持续时间PMs比homEMs和hetEMs约长 2 0 % ,而homEMs和hetEMs之间无统计学差异。结论 :给予相同剂量Eso后 ,对EMs和PMs者的平均抑酸作用强度相似 。AIM: To examine whether the effect of esomeprazole (Eso) on intragastric pH depends on CYP2C19 genotype status. METHODS: CYP2C19 genotype status for 2 mutations associated with the poor metabolizer phenotype was determined by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 27 healthy Chinese volunteers. After 5 days' administration of Eso 40 mg, po, qd, intragastric pH values were monitored for 24 h on both d 1 and d 5 of the study period. RESULTS: The 27 subjects were divided into 3 genotype groups including 10 homozygous extensive metabolisers (homEMs), 14 heterozygous extensive metabolisers (hetEMs) and 3 poor metabolisers (PMs) according to PCR-RFLP analysis. Oral administration of either a single dose of Eso 40 mg or repeated doses of Eso 40 mg once daily for 5 d did not produce statistically significant difference in the mean 24 h median pH values among the 3 genotype groups. With respect to the percentage of 24-hour monitoring period with pH>4, PMs showed about 20% longer duration of effect than homEMs and hetEMs on both d 1 and d 5 after dosing (P<0.05), while hetEMs was not significantly different from homEMs. CONCLUSION: The acid inhibitory effect of Eso is similar in potency among the subjects with different CYP2C19 genotypes, though different in duration between EMs and PMs.

关 键 词：埃索美拉唑 CYP2C19 基因分型 中国人 健康志愿者 胃内PH 

分 类 号：R96[医药卫生—药理学]