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

Abstract

SUMMARYAim: 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) 1 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 time were 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).

Comparative study of omeprazole, lansoprazole, pantoprazole and esomeprazole for symptom relief in patients with reflux esophagitis

“…A number of investigators have reported that earlier symptom relief and higher endoscopic healing rates have been obtained with PPI in comparison with H2-receptor antagonists (H2-RAs) [11,12] . The time period required to obtain maximal inhibition of gastric acid secretion is, however, reported to differ between PPI [13][14][15][16][17] . The time taken for the resolution of symptoms in patients with reflux esophagitis is, therefore, unlikely to be uniform in all PPI.…”

Upper digestive bleeding due to Dieulafoy's lesion during the postoperative period of aortocoronary bypass surgery in a patient treated with clopidogrel

“…Rabeprazole is the drug least metabolized via this enzyme route (10). Studies analyzing the capacity of the different PPIs to suppress gastric acid have shown that the mean pH value with the administration of rabeprazole is not influenced by the CYP2C19 genotypes (10)(11)(12).…”

Rabeprazole test for the diagnosis of gastro-oesophageal reflux disease: Results of a study in a primary care setting

“…The outcome of these rather rigorous inclusion criteria and design was a difficulty in fulfilling our initial goal of recruiting a large cohort of patients. Finally, from a number of candidate PPIs, we chose rabeprazole, since this drug has a number of potential advantages: (a) a rapid onset of action as shown by gastric pH monitoring studies [3,12,13] ; (b) a good safety profile; (c) a lack of drug interactions due to its specificity in terms of hepatic and non-hepatic metabolic pathways [4,5] ; and (d) its effectiveness in the treatment of some symptoms associated with GERD [14] . The results of our study are consistent with other studies of PPI tests which have without exception demonstrated the high sensitivity and poor specificity of this diagnostic approach [1] .…”

“…Similarly, when the target population for such PPI tests is considered, the lack of drug interference and the safety profile are both of most importance. In these respects, rabeprazole also displays some pharmacological advantages due to a partly non-hepatic metabolism and a linear response, which result in more predictable effects in terms of acid suppression [4,5] . We therefore aimed to deter mine the diagnostic value of the rabeprazole test in a population of patients followed up by general practitioners (GPs) for symptoms suspected to be reflux-related.…”