Potassium-Competitive Acid Blockers: New Opportunities of Antisecretory Therapy in Gastroesophageal Reflux Disease
https://doi.org/10.22416/1382-4376-2025-35-4-18-26
Abstract
Aim: to present modern data on the efficacy and safety of using potassium-competitive acid blockers (P-CAB) using tegoprazan as an example in patients with gastroesophageal reflux disease.
Key points. Potassium-competitive blockers of hydrochloric acid secretion, according to clinical studies, have demonstrated high clinical efficacy and safety in patients with gastroesophageal reflux disease. The advantages of this class of drugs include a faster and longer-lasting antisecretory effect, which does not depend on food intake, as well as the absence of the influence of genetic polymorphisms of the CYP2C19 isoenzyme on pharmacokinetics and the risk of drug interactions. In patients with nocturnal heartburn, the potassium-competitive acid blocker tegoprazan may be the drug of choice to achieve a faster and longer-lasting clinical effect and improve sleep quality. Tegoprazan is effective against nocturnal acid breakthroughs. In several studies, tegoprazan was superior to placebo and proton pump inhibitors (PPIs) in eliminating major symptoms in patients with nonerosive reflux disease and to PPIs in treating erosive esophagitis. P-CABs are considered the drugs of choice in the treatment of gastroesophageal reflux disease refractory to PPIs.
Conclusion. Further studies are needed, including in the Russian Federation, to confirm the high efficacy and safety of tegoprazan.
About the Authors
A. S. Trukhmanov
I.M. Sechenov First Moscow State Medical University (Sechenovskiy University)
Russian Federation
Russian Federation
Alexander S. Trukhmanov — Dr. Sci. (Med.), Professor of the Department of Propaedeutics of Internal Medicine, Gastroenterology and Hepatology of the N.V. Sklifosovsky Institute of Clinical Medicine
119435, Moscow, Pogodinskaya str., 1, build. 1
D. E. Rumyantseva
I.M. Sechenov First Moscow State Medical University (Sechenovskiy University)
Russian Federation
Russian Federation
Diana E. Rumyantseva — Cand. Sci. (Med.), Physician at the Department of Gastroenterology, V.Kh. Vasilenko Clinic of Internal Diseases Propaedeutics, Gastroenterology and Hepatology; Assistant of the Department of Propaedeutics of Internal Diseases, Gastroenterology and Hepatology
119435, Moscow, Pogodinskaya str., 1, build. 1
References
1. Nirwan J.S., Hasan S.S., Babar Z.U., Conway B.R., Ghori M.U. Global prevalence and risk factors of gastro-oesophageal reflux disease (GORD): Systematic review with meta-analysis. Sci Rep. 2020;10(1):5814. DOI: 10.1038/s41598-020-62795-1
2. Bordin D.S., Abdulkhakov R.А., Osipenko M.F., Solovyeva A.V., Abdulkhakov S.R., Kirilenko N.P., et al. Multicenter study of gastroesophageal reflux disease symptoms prevalence in outpatients in Russia. Terapevticheskii arkhiv. 2022;94(1):48–56. (In Russ.)]. DOI: 10.26442/00403660.2022.01.201322
3. Ivashkin V.T., Maev I.V., Trukhmanov A.S., Lapina T.L., Storonova O.A., Zayratyants O.V., et al. Recommendations of the Russian Gastroenterological Association in diagnosis and treatment of gastroesophageal reflux disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(4):70–97. (In Russ.)]. DOI: 10.22416/1382-4376-2020-30-4-70-97
4. Ivashkin V.T., Trukhmanov A.S., Maev I.V., Drapkina O.M., Livzan M.A., Martynov A.I., et al. Diagnosis and treatment of gastroesophageal reflux disease (Clinical guidelines of the Russian Gastroenterological Association, Russian Scientific Medical Society of Internal Medicine, Russian Society for the Prevention of Noncommunicable Diseases, Scientific Community for Human Microbiome Research). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2024;34(5):111–35. (In Russ.)]. DOI: 10.22416/1382-4376-2024-34-5-111-135
5. Eusebi L.H., Cirota G.G., Zagari R.M., Ford A.C. Global prevalence of Barrett’s oesophagus and oesophageal cancer in individuals with gastro-oesophageal reflux: A systematic review and meta-analysis. Gut. 2021;70(3):456–63. DOI: 10.1136/gutjnl-2020-321365
6. Shaheen N.J., Falk G.W., Iyer P.G., Gerson L.B; Ame- rican College of Gastroenterology. ACG clinical guideline: Diagnosis and management of Barrett’s esophagus. Am J Gastroenterol. 2016;111(1):30–50. DOI: 10.1038/ajg.2015.322
7. Malignant neoplasms in Russia in 2020 (morbidity and mortality). Kaprin A.D., Starinsky V.V., Shakhzadova A.O. (eds.). Moscow: P.A. Herzen Moscow Oncology Research Institute — Branch of the National Medical Research Center of Radiology, 2021. (In Russ.)].
8. Moroshek A.A., Bourmistrov M.V., Galkin S.V., Sigal I.E., Broder I.A., Ivanov A.I., et al. Pharmacoeconomic analysis of application of comprehensive algorithm for diagnostics and treatment of complicated gastroesophageal reflux disease in patients with esophageal hiatus hernia. Public health and healthcare. 2010;4:36–44. (In Russ.)].
9. Dean B.B., Aguilar D., Johnson L.F., McGuigan J.E., Orr W.C., Fass R., et al. Night-time and daytime atypical manifestations of gastro-oesophageal reflux disease: Frequency, severity and impact on health-related quality of life. Aliment Pharmacol Ther. 2008;27(4):327–37. DOI: 10.1111/j.1365-2036.2007.03574.x
10. Ivashkin V.T., Maev I.V., Trukhmanov A.S., Sheptulin A.A., Simanenkov V.I., Lapina T.L., et al. Deprescribing and optimal selection of proton pump inhibitors (Contributions of the 26th United Russian Gastroenterology Week). Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2020;30(6):7–18. (In Russ.)]. DOI: 10.22416/1382-4376-2020-30-6-7-18
11. Ivashkin V.T., Maev I.V., Trukhmanov A.S., Rumyantseva D.E. Modern achievements in the diagnosis and treatment of the refractory gastroesophageal reflux disease. Terapevticheskii Arkhiv. 2018;90(8):4–12. (In Russ.)]. DOI: 10.26442/terarkh20189084-12
12. Bytzer P., van Zanten S.V., Mattsson H., Wernersson B. Partial symptom-response to proton pump inhibitors in patients with non-erosive reflux disease or reflux oesophagitis — a post hoc analysis of 5796 patients. Aliment Pharmacol Ther. 2012;36(7):635–43. DOI: 10.1111/apt.12007
13. Cicala M., Emerenziani S., Guarino M.P., Ribolsi M. Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease. World J Gastroenterol. 2013;19(39):6529–35. DOI: 10.3748/wjg.v19.i39.6529
14. Chey W.D., Inadomi J.M., Booher A.M., Sharma V.K., Fendrick A.M., Howden C.W. Primary-care physicians’ perceptions and practices on the management of GERD: Results of a national survey. Am J Gastroenterol. 2005;100(6):1237–42. DOI: 10.1111/j.1572-0241.2005.41364.x
15. Gunaratnam N.T., Jessup T.P., Inadomi J., Lascewski D.P. Sub-optimal proton pump inhibitor dosing is prevalent in patients with poorly controlled gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2006;23(10):1473–7. DOI: 10.1111/j.1365-2036.2006.02911.x
16. Ronkainen J., Aro P., Storskrubb T., Johansson S.E., Lind T., Bolling-Sternevald E., et al. High prevalence of gastroesophageal reflux symptoms and esophagitis with or without symptoms in the general adult Swedish population: A Kalixanda study report. Scand J Gastroenterol. 2005;40(3):275–85. DOI: 10.1080/00365520510011579
17. Richter J.E., Kahrilas P.J., Johanson J., Maton P., Breiter J.R., Hwang C., et al; Esomeprazole Study Investigators. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: A randomized controlled trial. Am J Gastroenterol. 2001;96(3):656–65. DOI: 10.1111/j.15720241.2001.3600_b.x
18. Lightdale C.J., Schmitt C., Hwang C., Hamelin B. A multicenter, randomized, double-blind, 8-week comparative trial of low-dose esomeprazole (20 mg) and standard-dose omeprazole (20 mg) in patients with erosive esophagitis. Dig Dis Sci. 2006;51(5):852–7. DOI: 10.1007/s10620-005-9071-3
19. Higuchi K., Joh T., Nakada K., Haruma K. Is proton pump inhibitor therapy for reflux esophagitis sufficient?: A large real-world survey of Japanese patients. Intern Med. 2013;52(13):1447–54. DOI: 10.2169/internalmedicine.52.0349
20. Katz P.O., Johnson D.A., Levine D., Röhss K., Junghard O., Astrand M., et al. A model of healing of Los Angeles grades C and D reflux oesophagitis: Is there an optimal time of acid suppression for maximal healing? Aliment Pharmacol Ther. 2010;32(3):443–7. DOI: 10.1111/j.1365-2036.2010.04367.x
21. Peghini P.L., Katz P.O., Bracy N.A., Castell D.O. Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors. Am J Gastroenterol. 1998;93(5):763–7. DOI: 10.1111/j.1572-0241.1998.221_a.x
22. Han S., Choi H.Y., Kim Y.H., Nam J.Y., Kim B., Song G.S., et al. Randomised clinical trial: Safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple oral doses of tegoprazan (CJ-12420), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2019;50(7):751–9. DOI: 10.1111/apt.15438
23. Han S., Choi H.Y., Kim Y.H., Choi S., Kim S., Nam J.Y., et al. Comparison of pharmacodynamics between tegoprazan and dexlansoprazole regarding nocturnal acid breakthrough: A randomized crossover study. Gut Liver. 2023;17(1):92–9. DOI: 10.5009/gnl220050
24. Takahashi N., Take Y. Tegoprazan, a novel potassium-competitive acid blocker to control gastric acid secretion and motility. J Pharmacol Exp Ther. 2018;364(2):275–86. DOI: 10.1124/jpet.117.244202
25. Han S., Choi H.Y., Kim Y.H., Nam J.Y., Kim B., Song G.S., et al. Effect of food on the pharmacokinetics and pharmacodynamics of a single oral dose of tegoprazan. Clin Ther. 2021;43(8):1371–80. DOI: 10.1016/j.clinthera.2021.06.007
26. Yang E., Kim S., Kim B., Kim B., Kim Y., Park S.S., et al. Night-time gastric acid suppression by tegoprazan compared to vonoprazan or esomeprazole. Br J Clin Pharmacol. 2022;88(7):3288–96. DOI: 10.1111/bcp.15268
27. Han G.H., Kim S.J., Ko W.K., Hong J.B., Sheen S.H., Cho M.J., et al. Anti-Inflammatory effects of tegoprazan in lipopolysaccharide-stimulated bone-marrow- derived macrophages. Int J Mol Sci. 2023;24(19):14589. DOI: 10.3390/ijms241914589
28. Kim S.Y., Yoon J.H., Jung D.H., Kim G.H., Kim C.H., Lee S.K. Fexuprazan safeguards the esophagus from hydrochloric acid-induced damage by suppressing NLRP1/ Caspase-1/GSDMD pyroptotic pathway. Front Immunol. 2024;15:1410904. DOI: 10.3389/fimmu.2024.1410904
29. Kim M.G., Im Y.J., Lee J.H., Kim E.Y., Yeom S.W., Kim J.S. Comparison of hepatotoxicity of tegoprazan, a novel potassium-competitive acid blocker, with proton pump inhibitors using real-world data: A nationwide cohort study. Front Med (Lausanne). 2023;9:1076356. DOI: 10.3389/fmed.2022.1076356
30. Kim J.S., Seo S.I., Kang S.H., Lee S.K., Kim A.R., Park H.W., et al. Effects of tegoprazan versus esomeprazole on nighttime heartburn and sleep quality in gastroesophageal reflux disease: A multicenter double-blind randomized controlled trial. J Neurogastroenterol Motil. 2023;29(1):58–64. DOI: 10.5056/jnm22104
31. Kim S.H., Cho K.B., Chun H.J., Lee S.W., Kwon J.G., Lee D.H., et al. Randomised clinical trial: Comparison of tegoprazan and placebo in non-erosive reflux disease. Aliment Pharmacol Ther. 2021;54(4):402–11. DOI: 10.1111/apt.16477
32. Wang Y., Dai X., Zhang X. Network meta-analysis of comparing different dosages of potassium-competitive acid blocker with proton-pump inhibitor in acid-related disorders. Clin Transl Gastroenterol. 2024;15(11):e00776. DOI: 10.14309/ctg.0000000000000776
33. Seo S., Jung H.K., Gyawali C.P., Lee H.A., Lim H.S., Jeong E.S., et al. Treatment response with potassium-competitive acid blockers based on clinical phenotypes of gastroesophageal reflux disease: A systematic literature review and meta-analysis. J Neurogastroenterol Motil. 2024;30(3):259–71. DOI: 10.5056/jnm24024
34. Zhuang Q., Chen S., Zhou X., Jia X., Zhang M., Tan N., et al. Comparative efficacy of P-CAB vs proton pump inhibitors for Grade C/D esophagitis: A systematic review and network meta-analysis. Am J Gastroenterol. 2024;119(5):803–13. DOI: 10.14309/ajg.0000000000002714
35. Zhou X., Duan H., Li Q., Wang Q., Sun X. Efficacy and safety of potassium-competitive acid inhibitors in the treatment of gastroesophageal reflux: A systematic review and meta-analysis. Scand J Gastroenterol. 2024;59(7):788–97. DOI: 10.1080/00365521.2024.2349638
36. Lee K.J., Son B.K., Kim G.H., Jung H.K., Jung H.Y., Chung I.K., et al. Randomised phase 3 trial: Tegoprazan, a novel potassium-competitive acid blocker, vs. esomeprazole in patients with erosive oesophagitis. Aliment Pharmacol Ther. 2019;49(7):864–72. DOI: 10.1111/apt.15185
37. Zhu H., Xue Q., Song Y., Zhang Z., Li X., Lyu S., et al. Efficacy and safety of tegoprazan (LXI-15028) vs. esomeprazole in patients with erosive esophagitis: A multicenter, randomized, double-blind, non-inferiority phase – trial. Chin Med J (Engl). 2024. DOI: 10.1097/CM9.0000000000003276
38. Cho Y.K., Kim J.H., Kim H.S., Kim T.O., Oh J.H., Choi S.C., et al. Randomised clinical trial: Comparison of tegoprazan and lansoprazole as maintenance therapy for healed mild erosive oesophagitis. Aliment Pharmacol Ther. 2023;57(1):72–80. DOI: 10.1111/apt.17255
39. Shin C.M., Choi S.C., Cho J.W., Kim S.Y., Lee O.J., Kim D.H., et al. Comparison of tegoprazan and lansoprazole in patients with erosive esophagitis up to 4 weeks: A multi-center, randomized, double-blind, active-comparator phase 4 trial. Neurogastroenterol Motil. 2025;37(1):e14969. DOI: 10.1111/nmo.14969
40. Liu Y., Gao Z., Hou X. Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: A systematic review and network meta-analysis. Therap Adv Gastroenterol. 2024;17:17562848241251567. DOI: 10.1177/17562848241251567
41. Iwakiri K., Fujiwara Y., Manabe N., Ihara E., Kuribayashi S., Akiyama J., et al. Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021. J Gastroenterol. 2022;57(4):267–85. DOI: 10.1007/s00535-022-01861-z
42. Jung H.K., Tae C.H., Song K.H., Kang S.J., Park J.K., Gong E.J., et al.; Korean Society of Neurogastroenterology and Motility. 2020 Seoul Consensus on the diagnosis and management of gastroesophageal reflux disease. J Neurogastroenterol Motil. 2021;27(4):453–81. DOI: 10.5056/jnm21077
43. Goh K.L., Lee Y.Y., Leelakusolvong S., Makmun D., Maneerattanaporn M., Quach D.T., et al. Consensus statements and recommendations on the management of mild-to-moderate gastroesophageal reflux disease in the Southeast Asian region. JGH Open. 2021;5(8):855–63. DOI: 10.1002/jgh3.12602
Review
For citations:
Trukhmanov A.S., Rumyantseva D.E. Potassium-Competitive Acid Blockers: New Opportunities of Antisecretory Therapy in Gastroesophageal Reflux Disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2025;35(4):18-26. https://doi.org/10.22416/1382-4376-2025-35-4-18-26
Views:
6
Email this article 
