{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:07:33Z","timestamp":1791313653978,"version":"4.3.1"},"reference-count":89,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz, Poland","doi-asserted-by":"publisher","award":["503\/1-002-01\/503-11-001"],"award-info":[{"award-number":["503\/1-002-01\/503-11-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Polish Society for the Digestive Tract Neoplasms Prevention","award":["503\/1-002-01\/503-11-001"],"award-info":[{"award-number":["503\/1-002-01\/503-11-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Gastroesophageal reflux disease (GERD) is a prevalent chronic gastrointestinal disorder that affects a substantial proportion of the global population. It is characterized by the extensive backward flow of stomach contents into the esophagus, leading to troublesome symptoms and potential complications. Proton pump inhibitors (PPIs) have long been the cornerstone of pharmacological treatment for GERD, effectively suppressing gastric acid secretion. However, a substantial subset of patients, referred to as PPI-refractory GERD, experience inadequate symptom control despite optimal PPI therapy. GERD significantly impacts patients\u2019 quality of life, affecting domains, such as vitality, pain, and physical functioning. Consequently, there is an urgent need for alternative therapeutic strategies and novel pharmacologic agents to provide more effective, long-term relief. Emerging treatment options include potassium-competitive acid blockers (PCABs) like vonoprazan, which offer more potent and sustained inhibition of gastric acid secretion compared to traditional PPIs. Additionally, prokinetic agents such as itopride have gained attention due to their potential to improve GERD symptoms by enhancing gastrointestinal motility and accelerating gastric emptying. This article reviews the mechanisms of action, clinical efficacy, and potential of these novel therapeutic approaches in improving patient outcomes in GERD management. With the growing prevalence of PPI resistance and side effects, a personalized, multifaceted approach to treatment is becoming increasingly necessary to optimize care for patients with GERD.<\/jats:p>","DOI":"10.3390\/ph18050699","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T04:13:44Z","timestamp":1746764024000},"page":"699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Advances in Gastroesophageal Reflux Disease Management: Exploring the Role of Potassium-Competitive Acid Blockers and Novel Therapies"],"prefix":"10.3390","volume":"18","author":[{"given":"Katarzyna","family":"Hossa","sequence":"first","affiliation":[{"name":"Department of Digestive Tract Diseases, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-1807","authenticated-orcid":false,"given":"Ewa","family":"Ma\u0142ecka-Wojciesko","sequence":"additional","affiliation":[{"name":"Department of Digestive Tract Diseases, Medical University of Lodz, 90-419 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1111\/j.1572-0241.2006.00630.x","article-title":"The Montreal definition and classification of gastroesophageal reflux disease: A global evidence-based consensus","volume":"101","author":"Vakil","year":"2006","journal-title":"Am. J. Gastroenterol."},{"key":"ref_2","unstructured":"Gajewski, P., Jaeschke, R., Budaj, A., Le\u015bniak, W., Krenke, R., Mejza, F., Ni\u017cankowska-Mogilnicka, E., D\u0105browski, A., Hartleb, M., and Nowakowska-Du\u0142awa, E. (2023). Interna Szczeklika: Ma\u0142y Podr\u0119cznik 2023\/24, Medycyna Praktyczna."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.gastro.2017.07.045","article-title":"Presentation and epidemiology of gastroesophageal reflux disease","volume":"154","author":"Richter","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_4","first-page":"16196","article-title":"Diagnostic and therapeutic management in gastroesophageal reflux disease: Consensus of the Polish Society of Gastroenterology","volume":"132","author":"Marek","year":"2022","journal-title":"Pol. Arch. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"769","DOI":"10.2165\/00019053-200321110-00002","article-title":"The Impack of Treatment for Gastro-oesophageal Reflux Disease on Health-Related Quality of Life","volume":"21","author":"Prasad","year":"2003","journal-title":"Pharmacoeconomics"},{"key":"ref_6","unstructured":"Antunes, C., Aleem, A., and Curtis, S.A. (2025). Gastroesophageal Reflux Disease, StatPearls [Internet]."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.3748\/wjg.v28.i28.3608","article-title":"Potassium-competitive acid blockers and gastroesophageal reflux disease","volume":"28","author":"Leowattana","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_8","first-page":"CD002095","article-title":"Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease","volume":"2013","author":"Sigterman","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_9","first-page":"e67654","article-title":"Gastroesophageal Reflux Disease: New Insights and Treatment Approaches","volume":"16","author":"Tanvir","year":"2024","journal-title":"Cureus"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1080\/14656566.2020.1817385","article-title":"The pharmacotherapeutic management of gastroesophageal reflux disease (GERD)","volume":"22","author":"Chapelle","year":"2021","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100198","DOI":"10.1016\/j.crphar.2024.100198","article-title":"GERD: Latest update on acid-suppressant drugs","volume":"7","author":"Martini","year":"2024","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_12","first-page":"S43","article-title":"New-Generation Proton Pump Inhibitors: Overcoming the Limitations of Early-Generation Agents","volume":"13","author":"Robinson","year":"2001","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.14309\/ajg.0000000000001538","article-title":"ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease","volume":"117","author":"Katz","year":"2022","journal-title":"Am. J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1055\/a-2344-6282","article-title":"S2k guideline Gastroesophageal reflux disease and eosinophilic esophagitis of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS)","volume":"62","author":"Madisch","year":"2024","journal-title":"Z. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s00535-022-01861-z","article-title":"Evidence-based clinical practice guidelines for gastroesophageal reflux disease 2021","volume":"57","author":"Iwakiri","year":"2022","journal-title":"J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1053\/j.gastro.2017.07.049","article-title":"Management of Gastroesophageal Reflux Disease","volume":"154","author":"Gyawali","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1053\/gast.1997.v112.pm9178669","article-title":"Speed of healing and symptom relief in grade II to IV gastroesophageal reflux disease: A meta-analysis","volume":"112","author":"Chiba","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11894-020-0753-y","article-title":"Novel Therapies for Gastroesophageal Reflux Disease: Beyond Proton Pump Inhibitors","volume":"22","author":"Shibli","year":"2020","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.giec.2019.12.005","article-title":"Proton Pump Inhibitors: The Good, Bad, and Ugly","volume":"30","author":"Niec","year":"2020","journal-title":"Gastrointest. Endosc. Clin. N. Am."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.1001\/jama.2013.280490","article-title":"Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency","volume":"310","author":"Lam","year":"2013","journal-title":"JAMA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1111\/apt.13194","article-title":"Long-term safety of proton pump inhibitor therapy assessed under controlled, randomised clinical trial conditions: Data from the SOPRAN and LOTUS studies","volume":"41","author":"Attwood","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_22","first-page":"e52773","article-title":"Long-Term Use of Proton-Pump Inhibitors: Unravelling the Safety Puzzle","volume":"16","author":"Bhatnagar","year":"2024","journal-title":"Cureus"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1001\/archinternmed.2010.94","article-title":"Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: Results from the Women\u2019s Health Initiative","volume":"170","author":"Gray","year":"2010","journal-title":"Arch. Intern. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1001\/jamainternmed.2015.7193","article-title":"Proton pump inhibitor use and the risk of chronic kidney disease","volume":"176","author":"Lazarus","year":"2016","journal-title":"JAMA Intern. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.4292\/wjgpt.v2.i3.17","article-title":"Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all?","volume":"2","author":"Fohl","year":"2011","journal-title":"World J. Gastrointest. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/ajg.2012.108","article-title":"Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: Meta-analysis","volume":"107","author":"Kwok","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s00406-014-0554-0","article-title":"Risk of dementia in elderly patients with the use of proton pump inhibitors","volume":"265","author":"Haenisch","year":"2015","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1001\/jamaneurol.2015.4791","article-title":"Association of proton pump inhibitors with risk of dementia: A pharmacoepidemiological claims data analysis","volume":"73","author":"Gomm","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_29","first-page":"322","article-title":"Long-term Use of Proton-Pump Inhibitor Therapy","volume":"4","author":"Metz","year":"2008","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"646","DOI":"10.5009\/gnl20036","article-title":"Proton Pump Inhibitor-Related Gastric Mucosal Changes","volume":"15","author":"Kim","year":"2021","journal-title":"Gut Liver"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.pharmthera.2016.08.001","article-title":"Potassium-competitive acid blockers: Advanced therapeutic option for acid-related diseases","volume":"168","author":"Inatomi","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1756283X17745776","DOI":"10.1177\/1756283X17745776","article-title":"Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: Safety and clinical evidence to date","volume":"11","author":"Sugano","year":"2018","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"993","DOI":"10.14309\/ajg.0000000000003140","article-title":"The Role of P-CABs in GERD","volume":"120","author":"Howden","year":"2025","journal-title":"Am. J. Gastroenterol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.1038\/ctg.2015.18","article-title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Rising TAK-438 (Vonoprazan) Doses in Healthy Male Japanese\/non-Japanese Subjects","volume":"6","author":"Sakurai","year":"2015","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_35","unstructured":"Stewart, J. (2025, January 10). Voquezna FDA Approval History. Available online: https:\/\/www.drugs.com\/history\/voquezna.html."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/2589977515666230428140741","article-title":"Tegoprazan as a New Remedy for Gastrointestinal Diseases in Comparison with its Therapeutic Predecessors: A Mini-Review","volume":"16","author":"Anik","year":"2024","journal-title":"Curr. Drug Res. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1358\/dot.2020.56.11.3202811","article-title":"Tegoprazan to treat gastroesophageal reflux disease","volume":"56","author":"Mermelstein","year":"2020","journal-title":"Drugs Today"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s00228-023-03521-4","article-title":"Review of the clinical development of fexuprazan for gastroesophageal reflux-related disease","volume":"79","author":"Ramani","year":"2023","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1007\/s40265-023-01865-w","article-title":"Keverprazan Hydrochloride: First Approval","volume":"83","author":"Kang","year":"2023","journal-title":"Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s11894-024-00939-3","article-title":"Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments","volume":"26","author":"Scarpignato","year":"2024","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"334","DOI":"10.5056\/jnm18029","article-title":"Potent Potassium-competitive Acid Blockers: A New Era for the Treatment of Acid-related Diseases","volume":"24","author":"Oshima","year":"2018","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17562848221122623","DOI":"10.1177\/17562848221122623","article-title":"The role of vonoprazan in patients with erosive esophagitis","volume":"15","author":"Zhang","year":"2022","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/apt.15641","article-title":"Randomised trial of acid inhibition by vonoprazan 10\/20 mg once daily vs rabeprazole 10\/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study)","volume":"51","author":"Takeuchi","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/apt.13325","article-title":"Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects\u2014A randomised open-label cross-over study","volume":"42","author":"Sakurai","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3288","DOI":"10.1111\/bcp.15268","article-title":"Night-time gastric acid suppression by tegoprazan compared to vonoprazan or esomeprazole","volume":"88","author":"Yang","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1111\/apt.15438","article-title":"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","volume":"50","author":"Han","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_47","first-page":"273","article-title":"Is It Time for Noncontinuous Therapy for Gastroesophageal Reflux Disease?","volume":"20","author":"Udemba","year":"2024","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1177\/87551225231166531","article-title":"Vonoprazan: A New Potassium-Competitive Acid Blocker","volume":"39","author":"Phillips","year":"2023","journal-title":"J. Pharm. Technol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/cpdd.1009","article-title":"The Effect of Food on the Pharmacokinetics of the Potassium-Competitive Acid Blocker Vonoprazan","volume":"11","author":"Mulford","year":"2022","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1124\/jpet.111.185314","article-title":"Characterization of a novel potassium-competitive acid blocker of the gastric H,K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438)","volume":"339","author":"Shin","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1159\/000456072","article-title":"Efficacy of Vonoprazan for Proton Pump Inhibitor-Resistant Reflux Esophagitis","volume":"95","author":"Hoshino","year":"2017","journal-title":"Digestion"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000478255","article-title":"The Effects of Switching to Vonoprazan, a Novel Potassium-Competitive Acid Blocker, on Gastric Acidity and Reflux Patterns in Patients with Erosive Esophagitis Refractory to Proton Pump Inhibitors","volume":"96","author":"Yamashita","year":"2017","journal-title":"Digestion"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1080\/00365521.2018.1486883","article-title":"Long-term outcomes of patients with symptomatic gastroesophageal reflux disease treated with vonoprazan","volume":"53","author":"Shinozaki","year":"2018","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.kjms.2017.07.004","article-title":"Vonoprazan treatment improves gastrointestinal symptoms in patients with gastroesophageal reflux disease","volume":"33","author":"Shinozaki","year":"2017","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1136\/gut.41.4.452","article-title":"Helicobacter pylori independent chronological change in gastric acid secretion in the Japanese","volume":"41","author":"Kinoshita","year":"1997","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1007\/s00535-014-1031-2","article-title":"Time series analysis of gastric acid secretion over a 20-year period in normal Japanese men","volume":"50","author":"Iijima","year":"2015","journal-title":"J. Gastroenterol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1631\/jzus.B1000013","article-title":"Is alcohol consumption associated with gastroesophageal reflux disease","volume":"11","author":"Chen","year":"2010","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1136\/gut.2005.066464","article-title":"Helicobacter pylori eradication induces marked increase in H+, \/K+-adenosine triphosphatase expression without altering parietal cell number in human gastric mucosa","volume":"55","author":"Osawa","year":"2006","journal-title":"Gut"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/apt.15062","article-title":"Randomised clinical trial: Vonoprazan versus lansoprazole for the initial relief of heartburn in patients with erosive oesophagitis","volume":"49","author":"Oshima","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1136\/gutjnl-2019-318365","article-title":"Phase III, randomised, double-blind, multicentre study to evaluate the efficacy and safety of vonoprazan compared with lansoprazole in Asian patients with erosive oesophagitis","volume":"69","author":"Xiao","year":"2020","journal-title":"Gut"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1053\/j.gastro.2022.09.041","article-title":"Vonoprazan Versus Lansoprazole for Healing and Maintenance of Healing of Erosive Esophagitis: A Randomized Trial","volume":"164","author":"Laine","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/apt.17728","article-title":"Randomised clinical trial: Efficacy and safety of on-demand vonoprazan versus placebo for non-erosive reflux disease","volume":"58","author":"Fass","year":"2023","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"803","DOI":"10.14309\/ajg.0000000000002714","article-title":"Comparative Efficacy of P-CAB vs Proton Pump Inhibitors for Grade C\/D Esophagitis: A Systematic Review and Network Meta-analysis","volume":"119","author":"Zhuang","year":"2024","journal-title":"Am. J. Gastroenterol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.cgh.2024.08.004","article-title":"Vonoprazan as a Long-term Maintenance Treatment for Erosive Esophagitis: VISION, a 5-Year, Randomized, Open-label Study","volume":"23","author":"Uemura","year":"2025","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kang, S.H., Moon, H.S., Sung, J.K., Kim, S.M., Kim, K.B., Lee, S.W., Cho, Y.S., Bang, K.B., and Song, K.H. (2025). Assessment of the efficacy of on-demand tegoprazan therapy in gastroesophageal reflux disease through a randomized controlled trial. Sci. Rep., 15.","DOI":"10.1038\/s41598-024-84065-0"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e14969","DOI":"10.1111\/nmo.14969","article-title":"Comparison of Tegoprazan and Lansoprazole in Patients with Erosive Esophagitis up to 4\u2009Weeks: A Multi-Center, Randomized, Double-Blind, Active-Comparator Phase 4 Trial","volume":"37","author":"Shin","year":"2025","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1111\/apt.16477","article-title":"Randomised clinical trial: Comparison of tegoprazan and placebo in non-erosive reflux disease","volume":"54","author":"Kim","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"17562848231167858","DOI":"10.1177\/17562848231167858","article-title":"Incidence and type of adverse events in patients taking vonoprazan: A systematic review and meta-analysis","volume":"16","author":"Xu","year":"2023","journal-title":"Therap. Adv. Gastroenterol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/apt.18458","article-title":"Integrated Analysis of Vonoprazan Safety for Symptomatic Gastro-Oesophageal Reflux Disease or Erosive Oesophagitis","volume":"61","author":"Howden","year":"2025","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_70","first-page":"527","article-title":"Safety profile of vonoprazan compared with proton pump inhibitors: Insight from a pharmacovigilance study","volume":"75","author":"Kambara","year":"2020","journal-title":"Pharmazie"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1136\/gutjnl-2016-313312","article-title":"Influence of potassium-competitive acid blocker on the gut microbiome of Helicobacter pylori-negative healthy individuals","volume":"66","author":"Otsuka","year":"2017","journal-title":"Gut"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1103836","DOI":"10.3389\/fmicb.2022.1103836","article-title":"Butyrate producers, \u201cThe Sentinel of Gut\u201d: Their intestinal significance with and beyond butyrate, and prospective use as microbial therapeutics","volume":"13","author":"Singh","year":"2022","journal-title":"Front. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.celrep.2019.03.054","article-title":"Butyrate protects mice from Clostridium difficile-induced colitis through an HIF-1-Dependent mechanism","volume":"27","author":"Fachi","year":"2019","journal-title":"Cell Rep."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Ouyang, M.L., Zou, S.P., Cheng, Q., Shi, X., Zhao, Y.Z., and Sun, M.H. (2023). Effect of potassium-competitive acid blockers on human gut microbiota: A systematic review and meta-analysis. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1269125"},{"key":"ref_75","first-page":"60","article-title":"The efficacy and safety of itopride as an add-on therapy to a proton pump inhibitor in the treatment of gastroesophageal reflux disease","volume":"19","author":"Wiatrak","year":"2024","journal-title":"Prz. Gastroenterol."},{"key":"ref_76","first-page":"241","article-title":"Pathophysiology of gastro-oesophageal reflux disease","volume":"26","author":"Palmiero","year":"2006","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_77","first-page":"52","article-title":"Itopride in the treatment of gastrointestinal motor disorders","volume":"11","year":"2022","journal-title":"Terapia"},{"key":"ref_78","first-page":"350","article-title":"Virtue of adding prokinetics to proton pump inhibitors in the treatment of laryngopharyngeal reflux disease: Prospective study","volume":"40","author":"Ezzat","year":"2011","journal-title":"J. Otolaryngol. Head Neck Surg."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1046\/j.1365-2036.1998.00268.x","article-title":"The effect of mosapride, a novel prokinetic, on acid reflux variables in patients with gastro-oesophageal reflux disease","volume":"12","author":"Ruth","year":"1998","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_80","first-page":"1953","article-title":"A comparative prospective study to assess the clinical efficacy and safety of pantoprazole monotherapy versus pantoprazole and itopride dual therapy in patients with gastroesophageal reflux disease in a tertiary care hospital","volume":"5","author":"Mamatha","year":"2017","journal-title":"Int. J. Basic Clin. Pharmacol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1053\/j.gastro.2020.02.031","article-title":"IW-3718 Reduces Heartburn Severity in Patients with Refractory Gastroesophageal Reflux Disease in a Randomized Trial","volume":"158","author":"Vaezi","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/S0016-5085(75)80284-8","article-title":"Effect of bile salts on the ionic permeability of the esophageal mucosa and their role in the production of esophagitis","volume":"68","author":"DenBesten","year":"1975","journal-title":"Gastroenterology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10620-005-1282-0","article-title":"Esophageal visceral sensitivity to bile salts in patients with functional heartburn and in healthy control subjects","volume":"50","author":"Siddiqui","year":"2005","journal-title":"Dig. Dis. Sci."},{"key":"ref_84","first-page":"119","article-title":"Effect of bile salts and related compounds on esophageal mucosa","volume":"67","author":"Kivilaakso","year":"1981","journal-title":"Scand. J. Gastroenterol. Suppl."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1136\/gut.44.5.598","article-title":"Toxic bile acids in gastro-oesophageal reflux disease: Influence of gastric acidity","volume":"44","author":"Nehra","year":"1999","journal-title":"Gut"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1007\/s10620-006-8024-9","article-title":"Trypsin activity and bile acid concentrations in the esophagus after distal gastrectomy","volume":"51","author":"Kono","year":"2006","journal-title":"Dig. Dis. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1111\/j.1572-0241.2004.04171.x","article-title":"Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barrett\u2019s esophagus: Acid reflux, bile reflux, or both?","volume":"99","author":"Tack","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11894-020-00780-4","article-title":"Non-acid reflux: When it matters and approach to management","volume":"22","author":"Zikos","year":"2020","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.36740\/WLek202406124","article-title":"Innovative therapeutic strategies in the treatment of gastroesophageal reflux disease (GERD): A review of progress and perspectives","volume":"77","author":"Kucharczyk","year":"2024","journal-title":"Wiad. Lek."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/5\/699\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:29:54Z","timestamp":1760030994000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/5\/699"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,9]]},"references-count":89,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["ph18050699"],"URL":"https:\/\/doi.org\/10.3390\/ph18050699","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,9]]}}}