埃索美拉唑对健康志愿者抑制胃泌酸的药效学研究

目的　比较埃索美拉唑与雷贝拉唑对健康志愿者抑制胃泌酸的效果及安全性。方法　 36名健康志愿者随机分为两组 ,分别口服埃索美拉唑 4 0mg或雷贝拉唑 10mg ,每日 1次 ,连续 5d ,经过14d的洗脱期后 ,交叉口服雷贝拉唑 10mg或埃索美拉唑 4 0mg ,每日 1次 ,连续 5d。分别于服药首日及第 5天连续测定 2 4h胃内 pH ,并以PCR方法鉴定细胞色素 (CYP) 2C19基因型。 结果　埃索美拉唑组服药后首日最初 4、2 4h和第 5天 2 4h胃内pH >4 .0的时间百分比分别为 5 8.9%、73.7%和 84 .2 % ,显著高于雷贝拉唑组 (32 .1%、5 4 .8%和 76 .2 % ,P <0 .0 0 1) ;胃内 pH中位值分别为 4 .2 9、5 .6 0和 6 .38,亦显著高于雷贝拉唑组 (2 .88、4 .2 6和 5 .77,P≤ 0 .0 0 1)。服药后首日及第 5天pH >4 .0超过 16h的志愿者埃索美拉唑组百分率分别为 6 3.9%和 88.9% ,亦显著高于雷贝拉唑 (33.3%和 6 1.1% ,P <0 .0 5 )。36名志愿者中 2 8名CYP 2C19基因型为强代谢型 ,8名为弱代谢型。两药对强代谢型或弱代谢型者胃泌酸的抑制差异无显著性 (P >0 .0 5 )。服药期间两组均未发生明显不良反应。结论　埃索美拉唑和雷贝拉唑均具有较强的抑制胃酸分泌效应 ,但在抑酸速度、抑酸强度和维持时间方面 ,4 0mg埃索美拉唑优于 10mg雷贝拉唑。两药

Study of esomeprazole and rabeprazole on 24-hour intragastric acid control in healthy volunteers

Objective To compare the efficacy and tolerability of esomeprazole and rabeprazole on intragastric acid suppression in healthy volunteers. Methods Thirty six healthy volunteers (twenty six males and ten females) were enrolled and randomly divided into two groups. All the subjects were administrated either esomeprazole 40 mg or rabeprazole 10 mg once daily for 5 days and then cross over repeated dosing with a 14 day washout interval. Intragastric pH was monitored continuously for 24 hours on day 1 and day 5. CYP 2C19 genotypes were determined to differentiate the extensive metabolizers (EMs) from poor metabolizers (PMs) by PCR method. Results Percentage of intragastric pH> 4 was found significantly higher in esomeprazole group than in rabeprazole group during first 4 hours (58.9% vs 32.1%), 24 hours on day 1 (73.7% vs 54.8%) and 24 hours on day 5 (84.2% vs 76.2%) (P<0.001, respectively). There was also a significant differences of median intragastric pH between esomeprazole and rabeprazole during the first 4 hours (4.29 vs 2.88), day 1 (5.60 vs 4.26) and day 5 (6.38 vs 5.77) ( P <0.001, respectively). The percentage of intragastric pH> 4 for at least 16 hours on day 1 and day 5 was higher in esomeprazole group than in rabeprazole group (day 1 63.9% vs 33.3%, day 5 88.9% vs 61.1%, P <0.05 respectively). Of 36 subjects, 28 were EMs genotype and 8 PMs genotype. There was no statistical significance on intragastric pH between the PM and EM groups. Conclusion Both esomeprazole and rabeprazole had safe and therapeutic effect of acid suppression, while esomeprazole 40 mg revealed more effective and rapid response than rabeprazole 10 mg. There was no significant difference of intragastric acid control between EM and PM CYP 2C19 genotypes.