Relative potency of proton-pump inhibitors—comparison of effects on intragastric pH

Comparative potency of proton-pump inhibitors (PPIs) is an important clinical issue. Most available trials have compared the different PPIs at one or a few selected specific dosages, making it difficult to derive quantitative equivalence dosages. Here we derived PPI dose equivalents based on a comprehensive assessment of dose-dependent effects on intragastric pH. All available clinical studies reporting the effects of PPIs on mean 24-h intragastric pH were sought from electronic databases including Medline. Studies included were restricted to those targeting the Caucasian population, and healthy volunteers or gastroesophageal reflux disease (GERD) patients. The dose-effect relationships for mean 24-h intragastric pH and for percentage of time with pH > 4 in 24 h were analyzed for each PPI using pharmacodynamic modeling with NONMEM and a model integrating all available data. Fifty-seven studies fulfilled the inclusion criteria. Based on the mean 24-h gastric pH, the relative potencies of the five PPIs compared to omeprazole were 0.23, 0.90, 1.00, 1.60, and 1.82 for pantoprazole, lansoprazole, omeprazole, esomeprazole, and rabeprazole, respectively. Compared with healthy volunteers, patients with GERD needed a 1.9-fold higher dose and Helicobacter pylori-positive individuals needed only about 20% of the dose to achieve a given increase in mean 24-h intragastric pH. The present meta-analysis provides quantitative estimates on clinical potency of individual PPIs that may be helpful when switching between PPIs and for assessing the cost-effectiveness of specific PPIs. However, our estimates must be viewed with caution because only a limited dose range has been tested and not exactly the same study conditions were applied for the different substances.