5 within 2 h, even with a single oral dose of 200 mg In previous

5 within 2 h, even with a single oral dose of 200 mg. In previous studies on PPI, onset of antisecretory action was between 1 h and 2 h, and intragastric pH values at that time were below approximately 3–3.5,14,15 suggesting that revaprazan could be used as a drug for on-demand therapy in acid-related disease. Differences in find more antisecretory effects between days 1 and 7 were not significant, indicating that the antisecretory effect of revaprazan was near maximal on day 1. These findings are unique, compared with the actions of omeprazole or lansoprazole, which show low efficacy after

the first dose, with increasing antisecretory effect of steady-state conditions upon repeated, once-daily administration.16–18 This study can be used to define the dose of revaprazan. Antisecretory effects, such as median intragastric pH and mean percentage time of pH > 4, were not significantly different between

the 150-mg and 200-mg groups. RGFP966 cost However, the mean percentage time of pH > 4 for the 200-mg group on day 7 was significantly higher than that of the 100-mg group in the H. pylori-positive, H. pylori-negative and overall groups of subjects. Therefore, of all doses tested, 200 mg revaprazan might result in the most effective suppression of gastric acid secretion. The increase in the effect of PPI in the presence of H. pylori has been described.19 Revaprazan also showed an increased acid inhibitory effect in H. pylori-positive subjects compared with H. pylori-negative subjects in this study. The pharmacokinetic analysis of revaprazan on day 1 suggests that orally administered revaprazan was rapidly absorbed and eliminated.

Concentration–time profiles and pharmacokinetic characteristics of revaprazan on day 7 were similar to those on day 1. Half-life was short and was only 1.4–1.7 times longer on day 7 than for on day 1. Slightly increased values for the areas under the plasma concentration–time curves upon repeated administration might correspond with an increase in pharmacodynamic effect. This may indicate that repeated daily administration of revaprazan produced a further increase in pH and the duration of its elevation, demonstrating a lack of development of tolerance, a well-known disadvantage of H2-RA.20 However, we did not analyze the statistical correlation between concentration and pharmacological effect because our study was designed as a pharmacodynamic study; our aim was to investigate the inhibitory effect of revaprazan on gastric pH. It is difficult to make a precise comparison of the effects of revaprazan in this study with those of PPI in other studies because of differences in study design and subjects. However, revaprazan is comparable with PPI in its gastric acid suppressive effect.14,21,22 It must be taken into account that these studies did not directly compare PPI and revaprazan, but revaprazan showed near maximal effects on day 1 compared with PPI.

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