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.