Discerning the MOA of Vonoprazan in Gastric Acid Management

The mechanism of action (MOA) of vonoprazan is unique. Unlike PPIs, it typically does not need an acidic environment for activation.⁴ Instead, vonoprazangets accumulated in the acidic secretory canaliculus of parietal cells and competes with potassium ions for the reversible inhibition of hydrogen-potassium adenosine triphosphatases (H⁺/K⁺-ATPases).^1,5 This results in slow dissociation rate from H⁺/K⁺-ATPases ensuring prolonged acid suppression.¹

Non-ionic vonoprazan, when reduced in a strong acidic secretory canaliculi, inhibits its passive transport to the cytoplasm.¹ Consequently, it remains in the parietal cells for extended periods, allowing it to inhibit the H⁺/K⁺-ATPases that are activated by further stimulation of acid secretion.¹ Remarkably, vonoprazan’s inhibitory effect on H⁺/K⁺-ATPases is around 350 times greater than lansoprazole, a well-known PPI.⁵ Last but not least, the drug inhibits both active and inactive proton pumps, offering comprehensive acid control.⁴

Let’s hear to what Prof. Hidekazu Suzuki has to say about the mechanism of action of Vonoprazan in gastric acid management.

 

Conclusion

Vonoprazan has become the first-choice drug for diverse gastric acid complications due to superior MOA.³ It provides reversible binding to H⁺/K⁺-ATPases, does not need an acid milieu for activation, and inhibits both active and inactive proton pumps.^1,4,5This novel approach addresses the unmet needs posed by conventional PPIs, marking a significant advancement in the management of gastric acid-related diseases.

References

1. Oshima T, Miwa H. Potent potassium-competitive acid blockers: A new era for the treatment of acid-related diseases. J Neurogastroenterol Motil. 2018;24(3):334–344.
2. Herszényi L, Bakucz T, Barabás L, et al. Pharmacological approach to gastric acid suppression: Past, present, and future. Dig Dis. 2020;38(2):104–111.
3. Shinozaki S, Osawa H, Hayashi Y, et al. Long-term vonoprazan therapy is effective for controlling symptomatic proton pump inhibitor-resistant gastroesophageal reflux disease. Biomed Rep. 2021;14(3):32.
4. Veererathinakumar NK, Ananthy V, Codi RS, et al. Potassium-competitive acid blocker: A newer target in the treatment of acid peptic disorder. SBV J. Basic Clin. Appl. Health Sci. 2023;6(2):33–38.
5. Ishida M, Tsuchiya M, Naito J, et al. Vonoprazan-associated nephrotoxicity: Extensive real-world evidence from spontaneous adverse drug reaction reports. Kidney Int. 2022;102(3):666–668.

For the use of a registered medical practitioner, hospital or laboratory only.

 LMRC Code: GGI-CO-A1-AQS-300041558-APPEMC-G24-1178 DOI of 15/07/24 and DOE of 15/08/24