From the Guidelines
Vonoprazan is a potassium-competitive acid blocker (PCAB) that works by reversibly binding to the proton pump in the stomach, thereby blocking the exchange of hydrogen and potassium ions and reducing gastric acid secretion.
Mechanism of Action
- The mechanism of action of vonoprazan is distinct from that of proton pump inhibitors (PPIs), which bind covalently and irreversibly to the proton pump 1.
- Vonoprazan's ionic and reversible binding to the proton pump allows for a more rapid onset of action and a longer duration of acid suppression compared to PPIs 1.
- The drug's ability to block the access of potassium to the potassium-binding site of the pump results in a more profound acid suppression than PPIs 1.
Key Characteristics
- Vonoprazan is an acid-stable drug that does not require enteric coating, unlike PPIs which are acid-labile 1.
- It has a longer half-life (5-7 hours) compared to PPIs (1-2 hours), allowing for once-daily dosing and a more consistent acid suppression throughout the day 1.
- The timing of administration is independent of mealtimes, making it more convenient for patients compared to PPIs which need to be taken 30-60 minutes before meals 1.
From the FDA Drug Label
Vonoprazan suppresses basal and stimulated gastric acid secretion at the secretory surface of the gastric parietal cell through inhibition of the H+, K+-ATPase enzyme system in a potassium-competitive manner Because this enzyme is regarded as the acid (proton) pump within the parietal cell, vonoprazan has been characterized as a type of gastric proton-pump inhibitor, in that it blocks the final step of acid production.
The mechanism of action of Vonoprazan is through potassium-competitive inhibition of the H+, K+-ATPase enzyme system, which is the acid (proton) pump within the gastric parietal cell, thereby blocking the final step of acid production 2.
- Key points:
- Inhibition of acid secretion: Vonoprazan suppresses basal and stimulated gastric acid secretion.
- Potassium-competitive manner: Vonoprazan inhibits the H+, K+-ATPase enzyme system in a potassium-competitive manner.
- No activation by acid required: Vonoprazan does not require activation by acid to exert its effect.
From the Research
Mechanism of Action of Vonoprazan
- Vonoprazan is a potassium-competitive acid blocker (P-CAB) that works by competing with potassium on the proton pump to inhibit gastric acid secretion 3.
- It acts directly on H+,K+-ATPase irrespectively of its activity, providing a fast onset of action without requiring acid activation and specific administration timing 4.
- Vonoprazan prevents K+ from binding to gastric H+/K+-ATPase, resulting in reversible acid suppression 5.
Comparison with Proton Pump Inhibitors (PPIs)
- Vonoprazan demonstrates superior and more consistent acid suppression than PPIs, resulting in rapid and sustained symptom relief and mucosal healing 6.
- It has a more rapid, potent, and prolonged inhibition of acid secretion, including better nighttime acid control, and less antisecretory variability, compared with PPIs 4.
- Vonoprazan is effective in treating PPI-resistant gastroesophageal reflux disease (GERD), with higher eradication rates for Helicobacter pylori when used in combination therapies 6, 7.
Efficacy and Safety
- Clinical trials have shown the efficacy of vonoprazan in treating GERD, peptic ulcer disease, and H. pylori infection, with a favorable safety profile and fewer adverse effects compared to PPIs 6, 5, 7.
- Vonoprazan is well-tolerated, with common adverse effects including nasopharyngitis, diarrhea, constipation, flatulence, dyspepsia, headache, and abdominal pain 3.