Effects of rabeprazole, lansoprazole and omeprazole on intragastric pH in CYP2C19 extensive metabolizers.

Summary Aim : To investigate the inhibitory effects on gastric acid secretion of three proton pump inhibitors, omeprazole, lansoprazole and rabeprazole, using a three-way crossover design in healthy Helicobacter pylori -negative,S-mephenytoin 4′-hydroxylase (CYP2C19) homo- and hetero-extensive metabolizers. Methods : Eight healthy Japanese male volunteers were enrolled. After the administration of rabeprazole (10 mg/day), lansoprazole (30 mg/day) or omeprazole (20 mg/day), intragastric pH monitoring was commenced from 24 h before the first proton pump inhibitor dose, and continued for days 1–3 after proton pump inhibitor administration. The pH electrode was used for 48 h and changed just before pH monitoring on day 2. Results : For the administration of 10 mg/day rabeprazole, the mean ratios of the 24-h pH ≥ 3 holding timewere 5.7 ± 1.1%,13.6 ± 2.2%, 35.3 ± 2.7% and 62.8 ± 3.1% for the pre-treatment day and days 1, 2 and 3, respectively. The same ratios for lansoprazole (30 mg/day) were 5.7 ± 0.7%, 7.4 ± 1.5%, 13.6 ± 3.4% and 26.6 ± 4.9%; the same ratios for 20 mg/day omeprazole were 5.9 ± 0.9%, 6.1 ± 1.2%, 11.4 ± 2.8% and 16.4 ± 4.6%. The mean ratio of the 24-h pH ≥ 3 holding time of days 1–3 increased significantly compared to the pre-treatment day (P < 0.01) with the administration of rabeprazole and lansoprazole. The magnitude of inhibition of gastric acid secretion after rabeprazole administration was stronger than that after lansoprazole. A significant elevation of the mean ratio of the 24-h pH ≥ 3 holding time was demonstrated on days 2 and 3 with omeprazole ( P < 0.01). Conclusions : In H. pylori -negative CYP2C19 extensive metabolizers, rabeprazole (10 mg/day) shows a faster onset of rising intragastric pH and a stronger inhibition of gastric acid secretion than do lansoprazole (30 mg/day) or omeprazole (20 mg/day). [ABSTRACT FROM AUTHOR]