Li Zhao-Shen, Zhan Xian-Bao, Xu Guo-Ming, Cheng Neng-Neng, Liao Zhuan
Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
J Gastroenterol Hepatol. 2007 Jun;22(6):815-20. doi: 10.1111/j.1440-1746.2006.04709.x.
Esomeprazole is the S-isomer of omeprazole, with a stronger acid suppressive effect than omeprazole. This open, randomized crossover study was designed to evaluate the effect of esomeprazole and another proton-pump inhibitor, rabeprazole, on intragastric pH in healthy Chinese.
Thirty-six healthy volunteers (26 men and 10 women, aged between 20 and 31 years) were enrolled. Subjects were given either esomeprazole 40 mg (n = 18) or rabeprazole 10 mg (n = 18) orally once daily for 5 days during the first dosing period, then the other medicine at the set dosage for the second dosing period. The two periods were separated by a 14-day washout phase. The doses were chosen according to the State Food and Drug Administration of China for the treatment of acid-related diseases. Intragastric pH was continuously monitored for 24 h on days 1 and 5 of each dosing period. CYP2C19 genotypes were analyzed to identify the extensive metabolizers (EM) and poor metabolizers (PM).
The percentage of time with intragastric pH >4 was significantly higher (P < 0.001) in subjects receiving esomeprazole than in those receiving rabeprazole in the first 4 h after administration of the first dose (70.65% vs 44.87%), at 24 h on day 1 (73.7% vs 54.8%) and at 24 h on day 5 (84.2% vs 76.2%). The median intragastric pH was also higher in subjects receiving esomeprazole than in those receiving rabeprazole in the first 6 h, day 1 and day 5 (P <or= 0.001). The percentage of subjects with intragastric pH >4 for at least 16 h on day 1 (63.9% vs 33.3%) and on day 5 (88.9% vs 61.1%) was higher after administration of esomeprazole than after rabeprazole (both P < 0.05). On genotype analysis, 28 of the subjects were EM and eight were PM. Those who were PM tended to have a higher, albeit not statistically significant, percentage of time with intragastric pH >4 and the median 24-h intragastric pH than those who were EM. Both drugs were well tolerated.
Esomeprazole 40 mg orally once daily is more effective and faster in increasing intragastric pH than rabeprazole 10 mg orally once daily, and thus offers a potential for improved efficacy in acid-related diseases.
埃索美拉唑是奥美拉唑的S-异构体，其抑酸作用比奥美拉唑更强。本开放性随机交叉研究旨在评估埃索美拉唑和另一种质子泵抑制剂雷贝拉唑对健康中国人体内胃内pH值的影响。
招募了36名健康志愿者（26名男性和10名女性，年龄在20至31岁之间）。在第一个给药期，受试者每天口服一次40毫克埃索美拉唑（n = 18）或10毫克雷贝拉唑（n = 18），持续5天，然后在第二个给药期给予另一种药物的设定剂量。两个给药期之间间隔14天的洗脱期。所选剂量依据中国国家食品药品监督管理总局用于治疗酸相关性疾病的标准。在每个给药期的第1天和第5天，连续24小时监测胃内pH值。分析CYP2C19基因型以识别广泛代谢者（EM）和慢代谢者（PM）。
在首次给药后的前4小时（70.65% 对44.87%）、第1天24小时（73.7% 对54.8%）以及第5天24小时（84.2% 对76.2%），接受埃索美拉唑的受试者胃内pH值>4的时间百分比显著高于接受雷贝拉唑的受试者（P < 0.001）。在第1天和第5天的前6小时、第1天和第5天，接受埃索美拉唑的受试者胃内pH值中位数也高于接受雷贝拉唑的受试者（P ≤ 0.001）。在第1天（63.9% 对33.3%）和第5天（88.9% 对61.1%），埃索美拉唑给药后胃内pH值>4至少16小时的受试者百分比高于雷贝拉唑给药后（均P < 0.05）。基因分型分析显示，28名受试者为EM，8名受试者为PM。PM受试者胃内pH值>4的时间百分比以及24小时胃内pH值中位数虽无统计学意义但倾向于更高。两种药物耐受性均良好。
每日口服一次40毫克埃索美拉唑在提高胃内pH值方面比每日口服一次1毫克雷贝拉唑更有效且起效更快，因此在酸相关性疾病治疗中具有提高疗效的潜力。
