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

Aliment Pharmacol Ther 2011; 33: 845–854 Summary 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.