Figure 1.

Simplified schematic description: differences between ‘conventional’ proton-pump inhibitors (PPIs) (a) and vonoprazan (b). (a) The H⁺/K⁺-ATPase is located on the secretary membrane of parietal cells and maintains the acidity in the stomach. The enzyme is responsible for pumping H⁺ ions out of the cells into the canaliculi, in exchange for K⁺ ions. Conventional PPIs are absorbed in the small intestine and subsequently reach the gastric parietal cells where they are converted to their active forms upon acid exposure, and covalently bind to the H⁺/K⁺-ATPase. Since conventional PPIs are unstable in canaliculi and are rapidly degraded, they are not able to inhibit new proton pumps (PPs) that surface after administration of the drug. Thus they require a few days to reach their maximum effect. (b) Vonoprazan, a potassium-competitive acid blocker, does not require acid activation. Vonoprazan is rapidly absorbed in the small intestine and accumulates in the canalicular membranes of parietal cells, binding to H⁺/K⁺-ATPase in a K⁺-competitive manner. Vonoprazan is more stable than conventional PPIs in the canaliculi, allowing fast and stable inhibition of gastric acid secretion.