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  • Review Article
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Insights into the future of gastric acid suppression

Nature Reviews Gastroenterology & Hepatology volume 6, pages 524–532 (2009)Cite this article

Abstract

The development of effective acid-suppression therapy (particularly PPIs) has revolutionized the treatment of acid-related diseases. Despite the overall effectiveness of these agents, they have some shortcomings, including a delayed onset of action, incomplete acid suppression in the majority of patients, and the need for ingestion before a meal to achieve maximal efficacy. Attempts to overcome these issues have included the development of isomeric PPIs (such as esomeprazole), alterations in drug delivery (such as delayed-release dexlansoprazole), and combined therapy with nonenterically coated PPIs and antacids (such as 'naked' omeprazole combined with sodium biocarbonate). Other acid-suppression agents in development or in late-phase trials include potassium-competitive acid blockers, new histamine receptor 2 antagonists, and gastrin antagonists. Although these agents could potentially achieve complete gastric acid suppression, risks may be associated with this level of suppression, including enteric infections and malabsorption of nutrients such as vitamin B12, iron and calcium. This Review provides an update on the status of acid-suppression therapy and discusses directions for future research.

Key Points

  • Acid-suppression therapy can be improved to provide accelerated onset and prolonged duration of action, and avoid the need for timing of doses according to food intake

  • Isomeric PPIs, such as esomeprazole, have advantages over racemic mixtures for most (perhaps all) currently available agents

  • Delayed-release technologies, such as delayed-release dexlansoprazole, may improve the efficacy of PPI therapy

  • New agents with long half-lives, such as ilaprazole, tenatoprazole, potassium-competitive acid blockers, novel histamine receptor 2 antagonists, and gastrin antagonists, are under development and might have improved efficacy

  • Combining another agent, such as sodium bicarbonate, a histamine receptor 2 antagonist, cholecystokinin-receptor or gastrin-receptor antagonist, with a PPI may increase the efficacy of treatment

  • PPI therapy is generally safe; however, metabolic and infectious concerns and drug–drug interaction issues will need to be addressed as powerful agents with long durations of action are developed

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Figure 1: Parietal cells with proton pump activation and binding of PPIs to proton pumps.

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    Kenneth R. DeVault & Nicholas J. Talley

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K. R. DeVault is a Consultant for AstraZeneca and Takeda, and he receives financial support for research and education from Addex, AstraZeneca, Janssen and Takeda.

N. J. Talley is a Consultant for Astellas, AstraZeneca, Centocor, Eisai, Elsevier, Ferring, Focus Medical, Gilead, In2MedEd, Ironwood, McNeil Consumer, MedScape, Meritage, Metabolic, Microbia, Novartis, OptumHealth, Salix, SK Life Sciences, SteigerWald, The Journal of Medicine, Theravance and Wyeth. He receives financial support from Dynogen, GlaxoSmithKline and Tioga.

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DeVault, K., Talley, N. Insights into the future of gastric acid suppression. Nat Rev Gastroenterol Hepatol 6, 524–532 (2009). https://doi.org/10.1038/nrgastro.2009.125

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