Redefining Acid Suppression in Acid Peptic Disorders: The Emerging Role of Prazans.
Goenka Mahesh M, Ghoshal Uday C UC, Yadav Devesh D, Muthuswamy Hariharan H et al.
Acid peptic disorders (APDs) affect approximately 38% of the population in India and commonly present with overlapping phenotypes, including gastroesophageal reflux disease (GERD), dyspepsia, and peptic ulcer disease (PUD), necessitating uniform and sustained acid suppression. Proton pump inhibitors (PPIs) have several clinical limitations, including a delayed onset of action of 3-5 days, incomplete 24-hour acid control with nocturnal acid breakthrough, high nonresponse rates of approximately 40% in GERD and 37% in nonerosive reflux disease (NERD), and variability related to cytochrome P450 2C19 (CYP2C19) metabolism, meal dependency, and drug interactions. Collectively, these limitations contribute to inconsistent real-world efficacy. Mechanistic and pharmacodynamic superiority: Potassium-competitive acid blockers (P-CABs) directly and reversibly inhibit the H+/K+-ATPase without requiring acid activation, thereby enabling a rapid onset of action from the first dose. Inhibition of both active and inactive proton pumps provides continuous and sustained acid suppression. P-CABs offer true 24-hour intragastric pH control, including nocturnal control, with a higher parietal-cell concentration of approximately 100,000-fold compared with approximately 1,000-fold for PPIs. Their meal-independent administration, low CYP-related variability, and minimal potential for drug interactions allow a more predictable response across patient populations. Rapid onset, nocturnal control, and comorbidity advantages-Tegoprazan may be considered in the following clinical settings: symptomatic GERD and on-demand treatment of GERD/NERD, because its rapid onset of action within approximately 30 minutes may facilitate early symptom relief and flexible dosing; nocturnal acid breakthrough, because it provides nocturnal pH control, with an intragastric pH of ≥4 maintained for approximately 66% of the night; patients at cardiovascular risk receiving antiplatelet therapy, dual antiplatelet therapy, or atorvastatin, because its lower interaction potential involving CYP2C19 and CYP3A4 may reduce the risk of gastrointestinal bleeding and treatment failure related to dyslipidemia; and patients with renal or metabolic comorbidities, because it has shown favorable renal safety signals and a lower decline in serum creatinine levels. Potency, high acid burden, and eradication efficacy-Vonoprazan may be preferred in the following situations: refractory GERD after PPI failure, because its potent and sustained acid suppression may overcome an inadequate response to PPIs; severe GERD and other high-acid-burden states, because it provides consistent and prolonged intragastric pH elevation; Helicobacter pylori eradication, because it may serve as a preferred treatment backbone, with reported eradication rates of approximately 92.6% through sustained maintenance of an intragastric pH >6; nonsteroidal anti-inflammatory drug-associated ulcers, because it may reduce ulcer recurrence and the risk of gastrointestinal bleeding; complex or recurrent PUD, because its stronger acid suppression may support faster and more durable healing; and hepatic disease, because it has demonstrated favorable outcomes, with fewer liver-related complications than PPIs. Fexuprazan may be considered for extraesophageal reflux, including laryngopharyngeal reflux and atypical GERD, because it has been associated with improvements in reflux symptom indices and airway-related symptoms. Tegoprazan may be preferred when rapid symptom relief, nocturnal acid control, and a favorable drug-interaction profile are required. Vonoprazan may be preferred when maximal acid suppression and enhanced H. pylori eradication efficacy are needed. Fexuprazan may be considered for laryngopharyngeal reflux and other atypical or extraesophageal GERD phenotypes.