St. Mary's Hospital, McGill University, Westmount, Montreal, QC, Canada.
Aliment Pharmacol Ther. 2011 Apr;33(7):845-54. doi: 10.1111/j.1365-2036.2011.04580.x. Epub 2011 Jan 28.
Novel rabeprazole extended-release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients.
To evaluate the pharmacodynamics and pharmacokinetics of six rabeprazole-ER formulations vs. esomeprazole 40 mg and rabeprazole delayed-release (DR) 20 mg.
Helicobacter pylori-negative healthy subjects were randomised to receive one of eight treatments once daily for 5 days. Twenty-four-hour intragastric pH was monitored on days -1, 1 and 5. Rabeprazole plasma concentrations were measured on day 5.
A total of 248 subjects (N=31/group) were enrolled in the study. On day 5, rabeprazole-ER groups provided mean durations of 18.5-20.2 h (77.0-84.1% of 24-h) with intragastric pH >4.0 vs. esomeprazole 40 mg (15.9 h/66.1% of 24-h) and rabeprazole-DR 20 mg (15.2 h/63.2% of 24-h). A similar increase was observed on day 1. While percentage of daytime (8 am-10 pm) with intragastric pH >4.0 on day 5 was overall similar across the groups, percentage of night-time (10 pm-8 am) with intragastric pH >4.0 was higher with the rabeprazole-ER groups (57.0-72.4%) vs. esomeprazole 40 mg (32.8%) and rabeprazole-DR 20 mg (34.0%).
Rabeprazole-ER once daily for 5 days demonstrated a significantly longer duration of gastric acid suppression in 24 h vs. esomeprazole 40 mg and rabeprazole-DR 20 mg. The increase in acid suppression was predominantly due to prolonged acid suppression during the night-time; this was supported by the extended-release pharmacokinetic characteristics.
新型雷贝拉唑延长释放（ER）制剂的开发旨在为 GERD 患者提供更持久的胃酸抑制，并可能改善临床结果。
评估六种雷贝拉唑 ER 制剂与艾司奥美拉唑 40mg 和雷贝拉唑延迟释放（DR）20mg 的药效学和药代动力学。
幽门螺杆菌阴性的健康受试者随机接受每日一次的 8 种治疗方案中的一种，连续 5 天。在-1 天、1 天和 5 天监测 24 小时胃内 pH 值。在第 5 天测量雷贝拉唑的血浆浓度。
共有 248 名受试者（每组 31 名）入组研究。在第 5 天，雷贝拉唑 ER 组提供的胃内 pH 值>4.0 的时间分别为 18.5-20.2 小时（24 小时的 77.0-84.1%），与艾司奥美拉唑 40mg（15.9 小时/24 小时的 66.1%）和雷贝拉唑 DR 20mg（15.2 小时/24 小时的 63.2%）相比。在第 1 天也观察到了类似的增加。虽然第 5 天白天（8 点至 10 点）胃内 pH 值>4.0 的百分比在各组之间总体相似，但夜间（10 点至 8 点）胃内 pH 值>4.0 的百分比在雷贝拉唑 ER 组更高（57.0-72.4%），而艾司奥美拉唑 40mg 为 32.8%，雷贝拉唑 DR 20mg 为 34.0%。
雷贝拉唑 ER 每日一次，连续 5 天，与艾司奥美拉唑 40mg 和雷贝拉唑 DR 20mg 相比，24 小时胃内酸抑制的持续时间显著延长。酸抑制的增加主要是由于夜间酸抑制时间延长；这得到了延长释放药代动力学特征的支持。
