Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases

Abstract

Conventional proton pump inhibitors (PPIs) are used as a first-line therapy to treat acid-related diseases worldwide. However, they have a number of limitations including slow onset of action, influence by cytochrome P450 polymorphisms, unsatisfactory effects at night, and instability in acidic conditions. Alternative formulations of conventional PPIs have been developed to overcome these problems; however, these drugs have only introduced small advantages for controlling acid secretion compared to conventional PPIs. Potassium-competitive acid blockers (P-CABs) were developed and have beneficial effects including rapid, long-lasting, and reversible inhibition of the gastric hydrogen potassium ATPase, the proton pump of the stomach. Vonoprazan was recently innovated as a novel, orally active P-CAB. It is currently indicated for the treatment of gastric and duodenal ulcers, reflux esophagitis, and prevention of low-dose aspirin- or nonsteroidal anti-inflammatory drug-related gastric and duodenal ulcer recurrence in Japan. Vonoprazan does not require enteric coating as it is acid-stable, and it can be taken without food because it is quickly absorbed. Vonoprazan accumulates in parietal cells under both acidic and neutral conditions. It does not require an acidic environment for activation, has long-term stability at the site of action, and has satisfactory safety and tolerability. Thus, vonoprazan may address the unmet medical need for the treatment of acid-related diseases.

Efficacy of Vonoprazan for 48-Week Maintenance Therapy of Patients with Healed Reflux Esophagitis

“…VPZ was found to have a favorable safety and tolerability profile, which has also been observed in several other studies [16,17,42]. Mean morning fasting gastrin level after the administration of VPZ 20 mg for 4 weeks and VPZ 10 mg for 48 weeks was 977.2 pg/mL, which was similar to that in recent studies [18,19].…”

“…Although PPIs are used as the currently recommended first-line therapy for patients with GERD [5], these medications have a number of limitations including slow onset of action, unsatisfactory effects at night, influence by cytochrome P450 2C9 polymorphisms, and instability in acidic conditions [16,17,39,40]. The effect of VPZ 20 mg was attributed to its potent and rapid acid secretion-suppressive effects [41,42].…”

“…Vonoprazan (VPZ), a potassium-competitive acid blocker made in Japan, belongs to a novel class of acid suppressants that has been shown to provide quicker, steadier, and more potent inhibition of gastric acid secretion compared to PPIs [16,17].…”

Systematic review with meta‐analysis: Vonoprazan, a potent acid blocker, is superior to proton‐pump inhibitors for eradication of clarithromycin‐resistant strains of Helicobacter pylori

“…Placebo‐controlled studies have shown that macrolides drive resistance in populations . Thus, dual vonoprazan and amoxicillin therapy for 2 weeks is a promising alternative treatment …”

“…[33][34][35] Thus, dual vonoprazan and amoxicillin therapy for 2 weeks is a promising alternative treatment. [36][37][38] Nocturnal acid breakthrough (NAB) is another factor that may affect eradication rates. Kim et al 39 reported that the eradication rate among subjects without NAB was higher than that of patients with NAB.…”