Vonoprazan fumarate (TAK-438) is a novel P-CAB (potassium-competitive acid blocker) that reversibly inhibits H+/K+, ATPase.

TAK-438 has demonstrated effective and sustained inhibition of gastric acid secretion stimulated by histamine in both rats and dogs. This compound exhibits notable antisecretory activity through its high accumulation in gastric tissue and low clearance rate. Unlike PPIs (Proton Pump Inhibitors), TAK-438's efficacy is not influenced by the state of gastric secretion. It inhibits basal gastric acid secretion in a dose-dependent manner, with an ID50 value of 1.26 mg/kg. Intravenous administration of TAK-438 increases the pH of gastric perfusate in a dose-dependent way, maintaining the rise in pH for up to five hours. When treated with 1 mg/kg of TAK-438, the pH value reached a stable state after 90 minutes, with a maximum pH of 5.9.

TAK-438 inhibits the activity of gastric H+,K+-ATPase in a concentration-dependent manner. Its inhibitory effect remains almost unchanged under neutral (pH 7.5) and slightly acidic conditions (pH 6.5). Even at concentrations 500 times higher than its IC50 for gastric H+,K+-ATPase activity, TAK-438 does not inhibit Na+,K+-ATPase activity. TAK-438 inhibits gastric H+,K+-ATPase competitively with potassium (K+), with an inhibition constant (Ki) of 3 nM.