Zastaprazan, a Novel Potassium-Competitive Acid Blocker, for Acid-Related Disorders
Abstract
Proton pump inhibitors (PPIs) serve as the primary treatment for acid-related disorders, such as gastroesophageal reflux disease and peptic ulcer disease. Although PPIs are regarded as the first-line medication for acid suppression, they have notable limitations, including the need for acid-mediated activation, a short half-life and duration of action, and metabolic variability. Zastaprazan is a newly developed potassium-competitive acid blocker (P-CAB) that competitively and reversibly inhibits acid production and secretion. Like other P-CABs, zastaprazan exhibits pharmacodynamic and pharmacokinetic properties that differs significantly from those of PPIs. These differences offer potential advantages, such as rapid, robust, and long-standing acid suppression, the lack of CYP2C19 metabolism, and no need for conversion into an active form. Completed clinical trials of zastaprazan have demonstrated comparable or superior efficacy to that of PPIs for the healing of erosive esophagitis and gastric ulcers without concerning safety signals. Notably, in erosive esophagitis, zastaprazan 20 mg demonstrated faster healing at week 4 compared to esomeprazole 40 mg, whereas in gastric ulcers, zastaprazan 20 mg achieved a 100% healing rate at 8 weeks compared to 97.1% with lansoprazole 30 mg. Zastaprazan is approved in the Republic of Korea for the treatment of erosive esophagitis and gastric ulcer and is undergoing phase III clinical trials for the prevention of non-steroidal…
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