An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers

作者：Morelli G; Chen H^*; Rossiter G; Rege B; Lu Y

来源：Alimentary Pharmacology and Therapeutics, 2011, 33(7): 845-854.

DOI：10.1111/j.1365-2036.2011.04580.x

P>Background
Novel rabeprazole extended-release (ER) formulations were developed to provide prolonged gastric acid suppression and potentially improved clinical outcomes in GERD patients.
Aim
To evaluate the pharmacodynamics and pharmacokinetics of six rabeprazole-ER formulations vs. esomeprazole 40 mg and rabeprazole delayed-release (DR) 20 mg.
Methods
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.
Results
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%).
Conclusion
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 phamacokinetic characteristics.

• 出版日期2011-4-1
• 单位McGill