Role of Acid Suppression in Acid-related Diseases: Proton Pump Inhibitor and Potassium-competitive Acid Blocker

Abstract

Proton pump inhibitors are commonly utilized for the treatment of gastric acid-related diseases, such as gastroesophageal reflux disease, peptic ulcer disease, and Helicobacter pylori infection, and for the prevention of low-dose aspirin or nonsteroidal anti-inflammatory drug-induced peptic ulcers. Vonoprazan is a first-in-class potassium-competitive acid blocker, which has distinct advantages compared to other conventional proton pump inhibitors in terms of the efficacy for acid suppression. Due to its strong gastric acid suppression capabilities, vonoprazan serves as an effective drug for the treatment of gastroesophageal reflux disease and H. pylori infection.

<p>Vonoprazan Fumarate for the Treatment of Gastric Ulcers: A Short Review on Emerging Data</p>

“…PPIs are metabolized and consequently inactivated by cytochrome P450 (CYP) enzymes, mainly CYP2C19 and CYP3A4. 4 Despite their proven efficacy, PPIs present several limitations, such as delay in action onset (3-5 days), low bioavailability, nocturnal acid breakthrough, drug interactions and intake at appropriate times relative to meals. 1 Moreover, they are affected by marked interindividual variability of pharmacodynamics and clinical activity due to the existence of cytochrome polymorphisms.…”

“…Four distinct phenotypes were indeed described: a) extensive metabolizers (EM); b) intermediate metabolizers; c) ultra-rapid metabolizers; d) poor metabolizers. 4 CYP2C19 is the main responsible for the metabolism of omeprazole, lansoprazole and pantoprazole, whereas, to note, rabeprazole undergoes a mainly non-enzymatic metabolism with renal elimination of its metabolites. 4 Furthermore, an increasing prevalence of antibiotic resistance associated with treatment regimens including PPIs for the eradication of H. pylori infection has been described.…”

“…4 CYP2C19 is the main responsible for the metabolism of omeprazole, lansoprazole and pantoprazole, whereas, to note, rabeprazole undergoes a mainly non-enzymatic metabolism with renal elimination of its metabolites. 4 Furthermore, an increasing prevalence of antibiotic resistance associated with treatment regimens including PPIs for the eradication of H. pylori infection has been described. 1 Finally, recently, few safety concerns have been emphasized in different studies.…”

“…The first P-CAB used in clinical practice was revaprazan, available in South Korea and India since 2007. 4 Recently Takeda Pharmaceutical Company Limited (Japan) developed a novel and innovative P-CAB called vonoprazan, which is characterized by a potent, rapid and long-lasting effect, thanks to a reversible inhibition of gastric proton pump by a competitive block of the potassium binding site on the luminal surface of H + /K + ATPase. 1 Vonoprazan is a weak base, with a higher value of alkaline pKa (>9) than previous P-CABs and PPIs and, when exposed to acid, undergoes an instant protonation and accumulate at high concentrations in the canaliculi of parietal cells, thus determining higher stability in an acidic environment than PPIs.…”

A Triple-Drug Blister-Packaged Drug with Vonoprazan Improves First-Line Eradication of Helicobacter pylori in Elderly Patients: A Retrospective Propensity Score-Matched Cohort Study

“…The acid-inhibitory effect of VPZ is significantly stronger than that of conventional PPIs [3]. More acid inhibition is known to increase the efficacy of H. pylori eradication because an elevated gastric pH may induce H. pylori to re-enter the replicative state and become more susceptible to antibiotics [4][5][6][7]. Consequently, the overall first-line eradication rate by VPZ-containing triple therapy with CAM and AC is approximately 90%, regardless of the increased resistance to CAM [8][9][10], although CAM resistance has been shown to have a significantly negative impact on the eradication rate in randomized, double-blind trials using multivariate logistic regression analysis [8].…”