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- Materials and methods
Proton pump inhibitors (PPIs) are now considered to be the first-line treatment for gastro-oesophageal reflux disease (GERD). Treatment efficacy is strongly correlated with the degree and duration of acid suppression over 24 h.1,2 GERD patients who experience nocturnal symptoms may experience profound impairment of physical health, daytime function and emotional well-being, as demonstrated by measures of mental and physical well-being, pain and oesophageal erosion.3 Suppression of nocturnal acidity may be particularly important for symptom relief in such patients.
There are pharmacological differences among the PPIs after a single dose that may have implications for their clinical efficacy. For example, although all PPIs are strong inhibitors of gastric acid at steady state, rabeprazole may suppress acid output more potently after a single dose.4,5 Such pharmacological differences may also have implications for the control of nocturnal acidity.
Both pantoprazole and rabeprazole are used to treat patients with night-time reflux symptoms. Some authors have suggested that, as pantoprazole has a longer half-life than many other PPIs, it might be more effective at relieving nocturnal symptoms.3
Our study was designed to compare the antisecretory effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg in Helicobacter pylori-negative subjects who had a clinical diagnosis of GERD and a history of nocturnal heartburn. Twenty milligrams of rabeprazole and 40 mg of pantoprazole are the recommended daily doses of each drug for oesophagitis healing and symptom relief. Although there are numerous studies of the effect of PPIs on intragastric pH at steady state, there are few published reports of the pharmacodynamic effects on the first day of therapy.
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- Materials and methods
Overall, and during each time interval (including the overnight hours), a single oral dose of rabeprazole 20 mg increased intragastric pH significantly more than did pantoprazole 40 mg in GERD patients with a history of nocturnal heartburn. In addition, mean percentage time pH > 4 was significantly higher after rabeprazole than pantoprazole during the 24 h after dosing and in all time intervals analysed.
Our results are consistent with those of a previous study in healthy H. pylori-negative volunteers, which showed that a single dose of rabeprazole 20 mg maintained pH > 4 for a greater proportion of the 24 h after dosing than did pantoprazole 40 mg, lansoprazole 30 mg or omeprazole 20 mg.4 Furthermore, the authors showed that night-time pH (14–22 h after dosing) was higher after a single dose of rabepraozole 20 mg than pantoprazole 40 mg or omeprazole 20 mg.4 Our results are also compatible with those of a study in patients with gastric or duodenal ulcer, in which single doses of rabeprazole 10 mg yielded a significantly greater acid suppressant effect than did pantoprazole 40 mg or omeprazole 20 mg, as judged by nocturnal acid breakthrough and nocturnal alkaline amplitude.6
As the acid suppressant effect of rabeprazole 20 mg significantly exceeded that of pantoprazole 40 mg, it is clear that in our study population, oral rabeprazole was pharmacologically more than twice as potent as oral pantoprazole on an mg-per-mg basis. However, it should be noted that the results reported here apply only to single doses of the drugs. Only one study has directly compared the pharmacodynamic effects of repeated doses of rabeprazole and pantoprazole, as part of a crossover study comparing five PPIs in GERD patients.7 The results were compatible with our findings in that the effects on intragastric pH of 5 days’ treatment with rabeprazole 20 mg were numerically greater than those of pantoprazole 40 mg. However, the authors did not present the statistical significance of the differences.
One possible limitation of our study is its open-label design. However, the endpoint, intragastric pH, is an objective measurement; therefore, we do not believe that the open design is a serious limitation.
Our results are of potential clinical relevance to the use of rabeprazole at the start of continuous therapy in symptomatic patients with GERD, when, ideally, the first dose should have a profound effect. Our findings may also be relevant to the intermittent or on-demand use of rabeprazole in uncomplicated GERD. Such use requires a PPI with a substantial effect on intragastric pH that is sustained over the 24 h after a single dose. Studies of on-demand use of rabeprazole suggest that it controls symptoms effectively.8,9 National guidelines in the UK now recommend on-demand therapy for GERD, not only because it promotes patients’ involvement in the management of their disease, but also because it should be less expensive, as patients take an average of 0.4 tablets/day.10
Relief of nocturnal reflux requires a medication with an acid suppressant effect that is sustained into the overnight hours. In our study, a single dose of rabeprazole increased intragastric pH to a significantly greater extent than did pantoprazole during all time intervals up to 24 h after dosing. The difference between treatments was most marked in the 5- to 24-h period. Although pantoprazole has a slightly longer half-life than rabeprazole (1.2 h vs. 1.0 h), we found the effect of rabeprazole on intragastric pH to be more sustained, as demonstrated by the significantly greater percentage of time with pH > 3 and >4 after rabeprazole 20 mg than after pantoprazole 40 mg for all time intervals. If GERD patients were to take a single dose of these drugs during the first half of the day, rabeprazole might be expected to be the more effective treatment in preventing nocturnal heartburn. However, clinical trials would be needed to test that expectation.
In summary, in patients with GERD and nocturnal heartburn, we found that mean area under the intragastric pH–time curve (AUC) and the mean percentage time with pH > 3 and >4 were significantly higher after a single dose of rabeprazole 20 mg than after pantoprazole 40 mg in all time intervals analysed, including night time. These doses are the ones currently recommended for use in GERD. Rabeprazole was pharmacologically more potent than pantoprazole, by the oral route.