Beyond Proton Pump Inhibitors: Tegoprazan and the Emergence of Potassium-Competitive Acid Blockade
Abstract
The pharmacological suppression of gastric acid secretion remains central to the management of acid-related gastrointestinal disorders, including gastroesophageal reflux disease (GERD), peptic ulcer disease, and Helicobacter pylori infection. Proton pump inhibitors (PPIs) have long served as the mainstay of therapy due to their ability to irreversibly inhibit the gastric H⁺/K⁺-ATPase enzyme. However, their delayed onset of action, dependence on meal stimulated pump activation, interindividual variability in metabolism, and incomplete control of nocturnal acid secretion have highlighted the need for alternative therapeutic strategies. Potassium-competitive acid blockers (P-CABs) have emerged as a novel class of acid-suppressive agents that reversibly inhibit the proton pump by competing with potassium ions at its luminal binding site. This mechanism enables rapid, potent, and sustained acid suppression independent of acid activation. Several P-CABs, including vonoprazan, tegoprazan, fexuprazan, and revaprazan, have demonstrated promising pharmacological and clinical profiles. This review provides a comprehensive analysis of the evolution of acid suppression therapy, examines the mechanistic and pharmacological advantages of P-CABs, and presents a detailed comparison of available agents, with particular emphasis on tegoprazan. The clinical applications, safety considerations, and future directions of P-CAB therapy are also discussed, highlighting their potential to redefine…
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