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Effects of rabeprazole, lansoprazole and omeprazole on intragastric pH in CYP2C19 extensive metabolizers
Author(s) -
Saitoh T.,
Fukushima Y.,
Otsuka H.,
Hirakawa J.,
Mori H.,
Asano T.,
Ishikawa T.,
Katsube T.,
Ogawa K.,
Ohkawa S.
Publication year - 2002
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2002.01348.x
Subject(s) - lansoprazole , rabeprazole , omeprazole , proton pump inhibitor , cyp2c19 , gastric acid , medicine , crossover study , pharmacology , oral administration , helicobacter pylori , gastroenterology , chemistry , stomach , metabolism , placebo , alternative medicine , cytochrome p450 , pathology
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).