Comprehensive Report on Vonoprazan: A First-in-Class Potassium-Competitive Acid Blocker

I. Introduction: A Paradigm Shift in Acid Suppression Therapy

The global burden of acid-related gastrointestinal disorders, including gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and infections caused by the bacterium Helicobacter pylori, represents a significant and persistent challenge to public health and clinical practice.[1] For decades, the therapeutic landscape for these conditions has been dominated by proton pump inhibitors (PPIs), a class of drugs that includes well-known agents such as omeprazole and lansoprazole. The advent of PPIs marked a major advance in gastroenterology, offering effective acid suppression that became the standard of care worldwide.[4]

However, despite their widespread success, the pharmacological profile of PPIs is characterized by several well-documented limitations that can compromise their clinical utility. A fundamental aspect of their mechanism is the requirement for activation by acid within the parietal cell canaliculi. This necessitates that PPIs, which are unstable in acidic environments and require enteric coating, be administered 30 to 60 minutes before a meal to ensure they are present in the bloodstream when the proton pumps are maximally stimulated by food intake.[4] Furthermore, PPIs often require several days of repeated dosing to achieve their full therapeutic effect, a delay that can be suboptimal for patients seeking rapid symptom relief.[1] Perhaps one of the most significant clinical challenges is their inability to provide complete 24-hour acid control, with many patients experiencing nocturnal acid breakthrough, a phenomenon where gastric pH drops during the night despite appropriate dosing.[6] This incomplete suppression is linked to the irreversible nature of their binding to active proton pumps and the daily turnover of new, uninhibited pumps.