Skip to main content
SpringerLink
Log in

Potent Acid Suppression with PPIs and P-CABs: What’s New?

  • Stomach (P Malfertheiner, Section Editor)
  • Published:
Current Treatment Options in Gastroenterology Aims and scope Submit manuscript

Abstract

Purpose of the review

Acid suppression treatment has revolutionized the management of the acid-related disorders since the introduction of the H2-receptor antagonists (H2-RAs) and the proton pump inhibitors (PPIs). However, there has been increasing identification of needs for improvement in antisecretory therapy, especially in gastroesophageal reflux disease (GERD), the eradication of Helicobacter pylori (H. pylori), protection from aspirin (ASA) and non-steroidal inflammatory drug (NSAID) injury and the management of upper gastrointestinal (UGI) bleeding. There have also been increasing publications addressing safety concerns of antisecretory drugs.

Recent findings

The needs have been identified as shortcomings of the pharmacology of the delayed release-PPIs (DR-PPIs), which have short plasma half-lives, required to be given before a meal and show poor control of nocturnal acid secretion. New-generation PPIs have been developed, including dexlansoprazole modified release (MR), instant release omeprazole (IR-omeprazole), while metered release preparations such as Durasec™ or novel molecules such as tenatoprazole have also been developed and achieve superior control of intragastric pH especially at night. The major advance has been the development of the potassium channel acid blocking drugs, which block the K+,H+-ATPase K+ channel, are food independent, reversible, have a rapid onset of action, and maintain a prolonged and consistent elevation of intragastric pH. Vonoprazan, the first P-CAB, has so far been introduced only into a small number of Asian countries. Safety issues have been extensively addressed in numerous publications. This review sets the needs, individual new drug classes and key individual new treatments into clinical context.

Summary

Acid suppression treatment is reviewed including the pharmacology, the unmet clinical needs across the acid-related disorders, the place of new drug treatments, and where superiority exists. The safety of antisecretory drugs is broadly summarized with reference to several recent comprehensive reviews and set within the clinical context of patient management, particularly those on long-term treatment who are the greatest risk of some adverse events.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Hunt R. Acid suppression for reflux disease: "off-the-peg" or a tailored approach? Clin Gastroenterol Hepatol. 2012;10(3):210–3. https://doi.org/10.1016/j.cgh.2011.11.018.

    Article  PubMed  Google Scholar 

  2. Scarpignato C, Hunt RH. Editorial: towards extended acid suppression--the search continues. Aliment Pharmacol Ther. 2015;42(8):1027–9. https://doi.org/10.1111/apt.13384.

    Article  CAS  PubMed  Google Scholar 

  3. • Hunt RH, Scarpignato C. Potassium-competitive acid blockers (P-CABs): are they finally ready for prime time in acid-related disease? Clin Transl Gastroenterol. 2015;6:e119. https://doi.org/10.1038/ctg.2015.39 Thoughtful review on the potential role of P-CABs in acid-related diseases.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Burget DW, Chiverton SG, Hunt RH. Is there an optimal degree of acid suppression for healing of duodenal ulcers? A model of the relationship between ulcer healing and acid suppression. Gastroenterology. 1990;99(2):345–51.

    Article  CAS  Google Scholar 

  5. Howden CW, Jones DB, Peace KE, Burget DW, Hunt RH. The treatment of gastric ulcer with antisecretory drugs. Relationship of pharmacological effect to healing rates. Dig Dis Sci. 1988;33(5):619–24.

    Article  CAS  Google Scholar 

  6. Bell NJ, Burget D, Howden CW, Wilkinson J, Hunt RH. Appropriate acid suppression for the management of gastro-oesophageal reflux disease. Digestion. 1992;51(Suppl 1):59–67. https://doi.org/10.1159/000200917.

    Article  PubMed  Google Scholar 

  7. • Graham DY, Tansel A. Interchangeable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol. 2018;16(6):800–8 e7. https://doi.org/10.1016/j.cgh.2017.09.033 Interesting attempt to identify antisecretory equivalence among the currently available DR-PPIs.

    Article  CAS  PubMed  Google Scholar 

  8. Hunt RH. Review article: the unmet needs in delayed-release proton-pump inhibitor therapy in 2005. Aliment Pharmacol Ther. 2005;22(Suppl 3):10–9.

    Article  CAS  Google Scholar 

  9. Scarpignato C. Poor effectiveness of proton pump inhibitors in non-erosive reflux disease: the truth in the end! Neurogastroenterol Motil. 2012;24(8):697–704. https://doi.org/10.1111/j.1365-2982.2012.01977.x.

    Article  CAS  PubMed  Google Scholar 

  10. Yuan Y, Wang C, Yuan Y, Hunt RH. The proportion of patients who are free of reflux symptoms during the initial days of treatment with proton pump inhibitors (PPIs) in GERD trials: a meta-analysis. Gastroenterology. 2008;134(4, Suppl 1):A-174–5. https://doi.org/10.1016/s0016-5085(08)60812-4.

    Article  Google Scholar 

  11. Katz PO, Scheiman JM, Barkun AN. Review article: acid-related disease—what are the unmet clinical needs? Aliment Pharmacol Ther. 2006;23(Suppl 2):9–22. https://doi.org/10.1111/j.1365-2036.2006.02944.x.

    Article  CAS  PubMed  Google Scholar 

  12. Scarpignato C, Pelosini I. Review article: the opportunities and benefits of extended acid suppression. Aliment Pharmacol Ther. 2006;23(Suppl 2):23–34. https://doi.org/10.1111/j.1365-2036.2006.02945.x.

    Article  CAS  PubMed  Google Scholar 

  13. Dickman R, Maradey-Romero C, Gingold-Belfer R, Fass R. Unmet needs in the treatment of gastroesophageal reflux disease. J Neurogastroenterol Motil. 2015;21(3):309–19. https://doi.org/10.5056/jnm15105.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Goh KL, Choi MG, Hsu WP, Chun HJ, Mahachai V, Kachintorn U, et al. Unmet treatment needs of gastroesophageal reflux disease in Asia: gastroesophageal reflux disease in Asia Pacific survey. J Gastroenterol Hepatol. 2014;29(12):1969–75. https://doi.org/10.1111/jgh.12655.

    Article  PubMed  Google Scholar 

  15. Wright MR, Sharda R, Vaezi MF. Unmet needs in treating laryngo-pharyngeal reflux disease: where do we go from here? Expert Rev Gastroenterol Hepatol. 2016;10(9):995–1004. https://doi.org/10.1080/17474124.2016.1179576.

    Article  CAS  PubMed  Google Scholar 

  16. Yaghoobi M, Padol S, Yuan Y, Hunt RH. Impact of oesophagitis classification in evaluating healing of erosive oesophagitis after therapy with proton pump inhibitors: a pooled analysis. Eur J Gastroenterol Hepatol. 2010;22(5):583–90. https://doi.org/10.1097/MEG.0b013e328335d95d.

    Article  CAS  PubMed  Google Scholar 

  17. Fass R, Inadomi J, Han C, Mody R, O'Neil J, Perez MC. Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release. Clin Gastroenterol Hepatol. 2012;10(3):247–53. https://doi.org/10.1016/j.cgh.2011.11.021.

    Article  CAS  PubMed  Google Scholar 

  18. Yuan Y, Hunt RH. Evolving issues in the management of reflux disease? Curr Opin Gastroenterol. 2009;25(4):342–51. https://doi.org/10.1097/MOG.0b013e32832c1504.

    Article  PubMed  Google Scholar 

  19. Herregods TV, Troelstra M, Weijenborg PW, Bredenoord AJ, Smout AJ. Patients with refractory reflux symptoms often do not have GERD. Neurogastroenterol Motil. 2015;27(9):1267–73. https://doi.org/10.1111/nmo.12620.

    Article  CAS  Google Scholar 

  20. •• Yadlapati R, Vaezi MF, Vela MF, Spechler SJ, Shaheen NJ, Richter J, et al. Management options for patients with GERD and persistent symptoms on proton pump inhibitors: recommendations from an expert panel. Am J Gastroenterol. 2018;113(7):980–6. https://doi.org/10.1038/s41395-018-0045-4 Expert consensus providing an evidence-based decision making in PPI-refractory GERD.

    Article  PubMed  Google Scholar 

  21. •• Scarpignato C, Gatta L, Zullo A, Blandizzi C. SIF-AIGO-FIMMG Group; Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists, and the Italian Federation of General Practitioners. Effective and safe proton pump inhibitor therapy in acid-related diseases—a position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016;14(1):179. https://doi.org/10.1186/s12916-016-0718-z Comprehensive review on evidence-based PPI use.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lind T, Megraud F, Unge P, Bayerdorffer E, O'Morain C, Spiller R, et al. The MACH2 study: role of omeprazole in eradication of helicobacter pylori with 1-week triple therapies. Gastroenterology. 1999;116(2):248–53.

    Article  CAS  Google Scholar 

  23. Wheeldon TU, Hoang TT, Phung DC, Bjorkman A, Granstrom M, Sorberg M. Helicobacter pylori eradication and peptic ulcer healing: the impact of deleting the proton pump inhibitor and using a once-daily treatment. Aliment Pharmacol Ther. 2003;18(1):93–100.

    Article  CAS  Google Scholar 

  24. Hunt RH. pH and Hp—gastric acid secretion and Helicobacter pylori: implications for ulcer healing and eradication of the organism. Am J Gastroenterol. 1993;88(4):481–3.

    CAS  PubMed  Google Scholar 

  25. Furuta T, Graham DY. Pharmacologic aspects of eradication therapy for Helicobacter pylori infection. Gastroenterol Clin N Am. 2010;39(3):465–80. https://doi.org/10.1016/j.gtc.2010.08.007.

    Article  Google Scholar 

  26. Kim JI, Park SH, Kim JK, Chung IS, Chung KW, Sun HS. The effects of nocturnal acid breakthrough on Helicobacter pylori eradication. Helicobacter. 2002;7(6):331–6. https://doi.org/10.1046/j.1523-5378.2002.00105.x.

    Article  PubMed  Google Scholar 

  27. Sugimoto M, Furuta T, Shirai N, Kodaira C, Nishino M, Ikuma M, et al. Evidence that the degree and duration of acid suppression are related to Helicobacter pylori eradication by triple therapy. Helicobacter. 2007;12(4):317–23. https://doi.org/10.1111/j.1523-5378.2007.00508.x.

    Article  CAS  PubMed  Google Scholar 

  28. Yang JC, Lin CJ, Wang HL, Chen JD, Kao JY, Shun CT, et al. High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol. 2015;13(5):895–905.e5. https://doi.org/10.1016/j.cgh.2014.10.036.

    Article  CAS  PubMed  Google Scholar 

  29. Zullo A, Ridola L, Francesco VD, Gatta L, Hassan C, Alvaro D, et al. High-dose esomeprazole and amoxicillin dual therapy for first-line helicobacter pylori eradication: a proof of concept study. Ann Gastroenterol. 2015;28(4):448–51.

    PubMed  PubMed Central  Google Scholar 

  30. Plachetka J, Morelli G, Hines C, et al. Integrated gastric acidity can predict the prevention of naxopren-induced gastroduodenal pathology in normal subjects. Gastroenterology. 2003;124(Suppl 1):A510.

    Article  Google Scholar 

  31. Scarpignato C, Pelosini I. Prevention and treatment of non-steroidal anti-inflammatory drug-induced gastro-duodenal damage: rationale for the use of antisecretory compounds. Ital J Gastroenterol Hepatol. 1999;31(Suppl 1):S63–72.

    CAS  PubMed  Google Scholar 

  32. •• Scally B, Emberson JR, Spata E, Reith C, Davies K, Halls H, et al. Effects of gastroprotectant drugs for the prevention and treatment of peptic ulcer disease and its complications: a meta-analysis of randomised trials. Lancet Gastroenterol Hepatol. 2018;3(4):231–41. https://doi.org/10.1016/s2468-1253(18)30037-2 The most comprehensive meta-analysis to date on the prevention and treatment of PUD and its complications with PPIs and other gastroprotective compounds.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Rostom A, Moayyedi P, Hunt R. Canadian consensus guidelines on long-term nonsteroidal anti-inflammatory drug therapy and the need for gastroprotection: benefits versus risks. Aliment Pharmacol Ther. 2009;29(5):481–96. https://doi.org/10.1111/j.1365-2036.2008.03905.x.

    Article  CAS  PubMed  Google Scholar 

  34. Scarpignato C, Lanas A, Blandizzi C, Lems WF, Hermann M, Hunt RH. Safe prescribing of non-steroidal anti-inflammatory drugs in patients with osteoarthritis—an expert consensus addressing benefits as well as gastrointestinal and cardiovascular risks. BMC Med. 2015;13:55. https://doi.org/10.1186/s12916-015-0285-8.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Yeomans ND, Tulassay Z, Juhasz L, Racz I, Howard JM, van Rensburg CJ, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid suppression trial: ranitidine versus omeprazole for NSAID-associated ulcer treatment (ASTRONAUT) study group. New Engl J Med. 1998;338(11):719–26. https://doi.org/10.1056/nejm199803123381104.

    Article  CAS  PubMed  Google Scholar 

  36. Hawkey CJ, Karrasch JA, Szczepanski L, Walker DG, Barkun A, Swannell AJ, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus misoprostol for NSAID-induced ulcer management (OMNIUM) study group. New Engl J Med. 1998;338(11):727–34. https://doi.org/10.1056/nejm199803123381105.

    Article  CAS  PubMed  Google Scholar 

  37. Graham DY, Agrawal NM, Campbell DR, Haber MM, Collis C, Lukasik NL, et al. Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole. Arch Intern Med. 2002;162(2):169–75.

    Article  CAS  Google Scholar 

  38. Scarpignato C, Hunt RH. Nonsteroidal antiinflammatory drug-related injury to the gastrointestinal tract: clinical picture, pathogenesis, and prevention. Gastroenterol Clin N Am. 2010;39(3):433–64. https://doi.org/10.1016/j.gtc.2010.08.010.

    Article  Google Scholar 

  39. Scheiman JM. Unmet needs in non-steroidal anti-inflammatory drug-induced upper gastrointestinal diseases. Drugs. 2006;66(Suppl 1):15–21.

    Article  CAS  Google Scholar 

  40. •• Lanas A, Dumonceau JM, Hunt RH, Fujishiro M, Scheiman JM, Gralnek IM, et al. Non-variceal upper gastrointestinal bleeding. Nat Rev Dis Primers. 2018;4:18020. https://doi.org/10.1038/nrdp.2018.20 Comprehensive review by leading experts on the pathophysiology and management of upper GI bleeding.

    Article  PubMed  Google Scholar 

  41. Gralnek IM, Dumonceau JM, Kuipers EJ, Lanas A, Sanders DS, Kurien M, et al. Diagnosis and management of nonvariceal upper gastrointestinal hemorrhage: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy. 2015;47(10):a1–46. https://doi.org/10.1055/s-0034-1393172.

    Article  PubMed  Google Scholar 

  42. Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, et al. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Internal Med. 2010;152(2):101–13. https://doi.org/10.7326/0003-4819-152-2-201001190-00009.

    Article  Google Scholar 

  43. Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation. A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology. 1978;74(1):38–43.

    CAS  PubMed  Google Scholar 

  44. Vreeburg EM, Levi M, Rauws EA, Deventer SJ, Snel P, Bartelsman JW, et al. Enhanced mucosal fibrinolytic activity in gastroduodenal ulcer haemorrhage and the beneficial effect of acid suppression. Aliment Pharmacol Ther. 2001;15(5):639–46.

    Article  CAS  Google Scholar 

  45. Laine L, McQuaid KR. Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol. 2009;7(1):33–47. https://doi.org/10.1016/j.cgh.2008.08.016.

    Article  PubMed  Google Scholar 

  46. Lanas A, Artal A, Blas JM, Arroyo MT, Lopez-Zaborras J, Sainz R. Effect of parenteral omeprazole and ranitidine on gastric pH and the outcome of bleeding peptic ulcer. J Clin Gastroenterol. 1995;21(2):103–6.

    Article  CAS  Google Scholar 

  47. Scarpignato C, Pelosini I, Di Mario F. Acid suppression therapy: where do we go from here? Dig Dis. 2006;24(1–2):11–46. https://doi.org/10.1159/000091298.

    Article  PubMed  Google Scholar 

  48. Fass R, Frazier R. The role of dexlansoprazole modified-release in the management of gastroesophageal reflux disease. Ther Adv Gastroenterol. 2017;10(2):243–51. https://doi.org/10.1177/1756283x16681701.

    Article  CAS  Google Scholar 

  49. Oldfield Iv EC, Parekh PJ, Johnson DA. Dexlansoprazole: delayed-release orally disintegrating tablets for the treatment of heartburn associated with non-erosive gastroesophageal reflux disease and the maintenance of erosive esophagitis. Expert Rev Gastroenterol Hepatol. 2016;10:1083–9. https://doi.org/10.1080/17474124.2016.1230496.

    Article  CAS  Google Scholar 

  50. Morelli G, Chen H, Rossiter G, Rege B, Lu Y. An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers. Aliment Pharmacol Ther. 2011;33(7):845–54. https://doi.org/10.1111/j.1365-2036.2011.04580.x.

    Article  CAS  PubMed  Google Scholar 

  51. Howden CW. Review article: immediate-release proton-pump inhibitor therapy—potential advantages. Aliment Pharmacol Ther. 2005;22(Suppl 3):25–30. https://doi.org/10.1111/j.1365-2036.2005.02709.x.

    Article  CAS  PubMed  Google Scholar 

  52. Benetti C, Flammini L, Vivo V, Colombo P, Colombo G, Elviri L, et al. Esomeprazole immediate release tablets: gastric mucosa ex vivo permeation, absorption and antisecretory activity in conscious rats. J Control Release. 2016;239:203–10. https://doi.org/10.1016/j.jconrel.2016.08.032.

    Article  CAS  PubMed  Google Scholar 

  53. Banerjee R, Reddy DN, Guda NM, Kalpala R, Mahurkar S, Darisetty S, et al. Oral buffered esomeprazole is superior to i.v. pantoprazole for rapid rise of intragastric pH: a wireless pH metry analysis. J Gastroenterol Hepatol. 2010;25(1):43–7. https://doi.org/10.1111/j.1440-1746.2009.05994.x.

    Article  CAS  PubMed  Google Scholar 

  54. Goldstein JL, Howard KB, Walton SM, McLaughlin TP, Kruzikas DT. Impact of adherence to concomitant gastroprotective therapy on nonsteroidal-related gastroduodenal ulcer complications. Clin Gastroenterol Hepatol. 2006;4(11):1337–45. https://doi.org/10.1016/j.cgh.2006.08.016.

    Article  PubMed  Google Scholar 

  55. Dhillon S. Naproxen/esomeprazole fixed-dose combination: for the treatment of arthritic symptoms and to reduce the risk of gastric ulcers. Drugs Aging. 2011;28(3):237–48. https://doi.org/10.2165/11207150-000000000-00000.

    Article  CAS  PubMed  Google Scholar 

  56. Vynckier AK, De Beer M, Monteyne T, Voorspoels J, De Beer T, Remon JP, et al. Enteric protection of naproxen in a fixed-dose combination product produced by hot-melt co-extrusion. Int J Pharmac. 2015;491(1–2):243–9. https://doi.org/10.1016/j.ijpharm.2015.06.010.

    Article  CAS  Google Scholar 

  57. O'Connor JP, Taneike I, O'Morain C. Improving compliance with Helicobacter pylori eradication therapy: when and how? Ther Adv Gastroenterol. 2009;2(5):273–9. https://doi.org/10.1177/1756283x09337342.

    Article  Google Scholar 

  58. Kalfus IN, Raday G, Graham DY. Randomized placebo-controlled phase III study to assess the safety and efficacy of rifabutin triple therapy (RHB-105) for Helicobacter pylori infection in dyspepsia patients. Gastroenterology. 2017; 152(5). doi:https://doi.org/10.1016/s0016-5085(17)31130-7.

    Article  Google Scholar 

  59. Kinoshita Y, Kusano M, Iwakiri K, Fujishiro M, Tachikawa N, Haruma K. Efficacy and safety profile of Z-215 (azeloprazole sodium), a proton pump inhibitor, compared with rabeprazole sodium in patients with reflux esophagitis: a phase II, multicenter, randomized, double-blind, comparative study. Curr Ther Res Clin Exp. 2018;88:26–34. https://doi.org/10.1016/j.curtheres.2018.03.004.

    Article  PubMed  PubMed Central  Google Scholar 

  60. de Bortoli N, Martinucci I, Giacchino M, Blandizzi C, Marchi S, Savarino V, et al. The pharmacokinetics of ilaprazole for gastro-esophageal reflux treatment. Expert Opin Drug Metab Toxicol. 2013;9(10):1361–9. https://doi.org/10.1517/17425255.2013.813018.

    Article  CAS  PubMed  Google Scholar 

  61. Scarpignato C, Hunt RH. Proton pump inhibitors: the beginning of the end or the end of the beginning? Curr Opin Pharmacol. 2008;8(6):677–84. https://doi.org/10.1016/j.coph.2008.09.004.

    Article  CAS  PubMed  Google Scholar 

  62. Hunt RH, Armstrong D, Yaghoobi M, James C. The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjects. Aliment Pharmacol Ther. 2010;31(6):648–57. https://doi.org/10.1111/j.1365-2036.2009.04219.x.

    Article  CAS  PubMed  Google Scholar 

  63. Kodama K, Fujisaki H, Kubota A, Kato H, Hirota K, Kuramochi H, et al. E3710, a new proton pump inhibitor, with a long-lasting inhibitory effect on gastric acid secretion. J Pharmacol Exp Ther. 2010;334(2):395–401. https://doi.org/10.1124/jpet.110.167783.

    Article  CAS  PubMed  Google Scholar 

  64. Toda R, Shiramoto M, Komai E, Yoshii K, Hirayama M, Kawabata Y. Pharmacokinetics and pharmacodynamics of azeloprazole sodium, a novel proton pump inhibitor, in healthy Japanese volunteers. J Clin Pharmacol. 2018;58(4):425–33. https://doi.org/10.1002/jcph.1038.

    Article  CAS  PubMed  Google Scholar 

  65. Cheng D, Dai X, Zhang Y, Wu Y, Shi C, Ma X, et al. Determination of anaprazole in human plasma by LC-MS/MS in pharmacokinetic study. Acta Pharmac Sin. 2016;51(12):1885–90.

    Google Scholar 

  66. Wulandari AS, Tandrasasmita OM, Tjandrawinata RR. Bioactive fraction DLBS2411 from Cinnamomum burmanii, (nees and t. nees) blume as colon and gastroprotector by stimulating muc5ac and cyclooxygenase-2 gene expression. Int J Pharmacy Pharmac Sci. 2016;8(8):202–7.

    CAS  Google Scholar 

  67. Huang JQ, Hunt RH. pH, healing rate, and symptom relief in patients with GERD. Yale J Biol Med. 1999;72(2–3):181–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Inatomi N, Matsukawa J, Sakurai Y, Otake K. Potassium-competitive acid blockers: advanced therapeutic option for acid-related diseases. Pharmacol Ther. 2016;168:12–22. https://doi.org/10.1016/j.pharmthera.2016.08.001.

    Article  CAS  PubMed  Google Scholar 

  69. Kim HK, Park SH, Cheung DY, Cho YS, Kim JI, Kim SS, et al. Clinical trial: inhibitory effect of revaprazan on gastric acid secretion in healthy male subjects. J Gastroenterol Hepatol. 2010;25(10):1618–25. https://doi.org/10.1111/j.1440-1746.2010.06408.x.

    Article  CAS  PubMed  Google Scholar 

  70. Chung IS, Choi MG, Park S-H, Kim S-K, Chang R, Hyun J-H, et al. Revaprazan (Revanex®), a novel acid pump antagonist, for duodenal ulcer: results of a double-blind, randomized, parallel, multi-center phase III clinical trial. Korean J Gastrointest Endosc. 2005;31(1):17–24.

    Google Scholar 

  71. Chang R, Chung IS, Park S-H, Kim S-K, Reyol Choi S-R, Song G-A, et al. Phase III clinical trial of Revaprazan (Revanex®) for gastric ulcer. Korean J Gastrointest Endosc. 2007;34(6):312–9.

    Google Scholar 

  72. Kahrilas PJ, Dent J, Lauritsen K, Malfertheiner P, Denison H, Franzen S, et al. A randomized, comparative study of three doses of AZD0865 and esomeprazole for healing of reflux esophagitis. Clin Gastroenterol Hepatol. 2007;5(12):1385–91. https://doi.org/10.1016/j.cgh.2007.08.014.

    Article  CAS  PubMed  Google Scholar 

  73. Dent J, Kahrilas PJ, Hatlebakk J, Vakil N, Denison H, Franzen S, et al. A randomized, comparative trial of a potassium-competitive acid blocker (AZD0865) and esomeprazole for the treatment of patients with nonerosive reflux disease. Am J Gastroenterol. 2008;103(1):20–6. https://doi.org/10.1111/j.1572-0241.2007.01544.x.

    Article  CAS  PubMed  Google Scholar 

  74. Garnock-Jones KP. Vonoprazan: first global approval. Drugs. 2015;75(4):439–43. https://doi.org/10.1007/s40265-015-0368-z.

    Article  CAS  PubMed  Google Scholar 

  75. Shin JM, Inatomi N, Munson K, Strugatsky D, Tokhtaeva E, Vagin O, et al. 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-methyl methanamin e monofumarate (TAK-438). J Pharmacol Exp Ther. 2011;339(2):412–20. https://doi.org/10.1124/jpet.111.185314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. • Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokin. 2016;55(4):409–18. https://doi.org/10.1007/s40262-015-0326-7 Detailed review on the pharmacokinetics and pharmacodynamics of the first P-CAB, vonoprazan.

    Article  CAS  Google Scholar 

  77. Otake K, Sakurai Y, Nishida H, Fukui H, Tagawa Y, Yamasaki H, et al. Characteristics of the novel potassium-competitive acid blocker vonoprazan fumarate (TAK-438). Adv Ther. 2016;33(7):1140–57. https://doi.org/10.1007/s12325-016-0345-2.

    Article  CAS  PubMed  Google Scholar 

  78. Martinucci I, Blandizzi C, Bodini G, Marabotto E, Savarino V, Marchi S, et al. Vonoprazan fumarate for the management of acid-related diseases. Expert Opin Pharmacother. 2017;18(11):1145–52. https://doi.org/10.1080/14656566.2017.1346087.

    Article  CAS  PubMed  Google Scholar 

  79. Yang X, Li Y, Sun Y, Zhang M, Guo C, Mirza IA, et al. Vonoprazan: a novel and potent alternative in the treatment of acid-related diseases. Dig Dis Sci. 2018;63(2):302–11. https://doi.org/10.1007/s10620-017-4866-6.

    Article  CAS  PubMed  Google Scholar 

  80. Sugano K. Vonoprazan fumarate, a novel potassium-competitive acid blocker, in the management of gastroesophageal reflux disease: safety and clinical evidence to date. Ther Adv Gastroenterol. 2018;11:1756283x17745776. https://doi.org/10.1177/1756283x17745776.

    Article  Google Scholar 

  81. Sakurai Y, Nishimura A, Kennedy G, Hibberd M, Jenkins R, Okamoto H, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of single rising TAK-438 (vonoprazan) doses in healthy male Japanese/non-Japanese subjects. Clin Transl Gastroenterol. 2015;6:e94. https://doi.org/10.1038/ctg.2015.18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Jenkins H, Sakurai Y, Nishimura A, Okamoto H, Hibberd M, Jenkins R, et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of TAK-438 (vonoprazan), a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2015;41(7):636–48. https://doi.org/10.1111/apt.13121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Kagami T, Sahara S, Ichikawa H, Uotani T, Yamade M, Sugimoto M, et al. Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype. Aliment Pharmacol Ther. 2016;43(10):1048–59. https://doi.org/10.1111/apt.13588.

    Article  CAS  PubMed  Google Scholar 

  84. Ohkuma K, Iida H, Inoh Y, Kanoshima K, Ohkubo H, Nonaka T, et al. Comparison of the early effects of vonoprazan, lansoprazole and famotidine on intragastric pH: a three-way crossover study. J Clin Biochem Nutr. 2018;63(1):80–3. https://doi.org/10.3164/jcbn.17-128.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Sakurai Y, Mori Y, Okamoto H, Nishimura A, Komura E, Araki T, et al. Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects—a randomised open-label cross-over study. Aliment Pharmacol Ther. 2015;42(6):719–30. https://doi.org/10.1111/apt.13325.

    Article  CAS  PubMed  Google Scholar 

  86. Yuan Y, Hunt RH. Intragastric pH holding time of pH <4 predicts low erosive esophagitis (EE) healing rate. Gastroenterology. 2010;138(Suppl 1):S-651.

    Google Scholar 

  87. Yuan Y, Hunt RH. An updated model of intragastric pH and erosive esophagitis (EE) healing using 24-hour intragastric pH values to predict EE healing: validation by data from TAK-390MR. Gastroenterology. 2009;136(Suppl 1):A440–A1.

    Google Scholar 

  88. Ashida K, Sakurai Y, Nishimura A, Kudou K, Hiramatsu N, Umegaki E, et al. Randomised clinical trial: a dose-ranging study of vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the treatment of erosive oesophagitis. Aliment Pharmacol Ther. 2015;42(6):685–95. https://doi.org/10.1111/apt.13331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ashida K, Sakurai Y, Hori T, Kudou K, Nishimura A, Hiramatsu N, et al. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther. 2016;43(2):240–51. https://doi.org/10.1111/apt.13461.

    Article  CAS  PubMed  Google Scholar 

  90. Hoshino S, Kawami N, Takenouchi N, Umezawa M, Hanada Y, Hoshikawa Y, et al. Efficacy of vonoprazan for proton pump inhibitor-resistant reflux esophagitis. Digestion. 2017;95(2):156–61. https://doi.org/10.1159/000456072.

    Article  CAS  PubMed  Google Scholar 

  91. Ashida K, Iwakiri K, Hiramatsu N, Sakurai Y, Hori T, Kudou K, et al. Maintenance for healed erosive esophagitis: phase III comparison of vonoprazan with lansoprazole. World J Gastroenterol. 2018;24(14):1550–61. https://doi.org/10.3748/wjg.v24.i14.1550.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Kinoshita Y, Sakurai Y, Shiino M, Kudou K, Nishimura A, Miyagi T, et al. Evaluation of the efficacy and safety of Vonoprazan in patients with nonerosive gastroesophageal reflux disease: a phase III, randomized, double-blind, placebo-controlled, multicenter study. Curr Ther Res Clin Exp. 2016;81-82:1–7. https://doi.org/10.1016/j.curtheres.2016.12.001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Niikura R, Yamada A, Hirata Y, Hayakawa Y, Takahashi A, Shinozaki T et al. Efficacy of Vonoprazan for Gastroesophageal Reflux Symptoms in Patients with Proton Pump Inhibitor-resistant Non-erosive Reflux Disease. Intern Med (Tokyo, Japan). 2018. doi:https://doi.org/10.2169/internalmedicine.0492-17.

    Article  Google Scholar 

  94. Kawami N, Hoshino S, Hoshikawa Y, Takenouchi N, Umezawa M, Hanada Y, et al. Pathogenesis of potassium-competitive acid blocker-resistant non-erosive reflux disease. Digestion. 2018;98(3):194–200. https://doi.org/10.1159/000488530.

    Article  CAS  PubMed  Google Scholar 

  95. Thung I, Aramin H, Vavinskaya V, Gupta S, Park JY, Crowe SE, et al. Review article: the global emergence of Helicobacter pylori antibiotic resistance. Aliment Pharmacol Ther. 2016;43(4):514–33. https://doi.org/10.1111/apt.13497.

    Article  CAS  PubMed  Google Scholar 

  96. Gatta L, Scarpignato C. Editorial: Helicobacter pylori resistance and sequential therapy-authors’ reply. Aliment Pharmacol Ther. 2018;48(1):96–7. https://doi.org/10.1111/apt.14676.

    Article  CAS  PubMed  Google Scholar 

  97. Jung YS, Kim EH, Park CH. Systematic review with meta-analysis: the efficacy of vonoprazan-based triple therapy on Helicobacter pylori eradication. Aliment Pharmacol Ther. 2017;46(2):106–14. https://doi.org/10.1111/apt.14130.

    Article  CAS  PubMed  Google Scholar 

  98. Dong SQ, Singh TP, Wei X, Yao H, Wang HL. Review: a Japanese population-based meta-analysis of vonoprazan versus PPI for Helicobacter pylori eradication therapy: Is superiority an illusion? Helicobacter. 2017; 22(6). doi:https://doi.org/10.1111/hel.12438.

    Article  Google Scholar 

  99. Li M, Oshima T, Horikawa T, Tozawa K, Tomita T, Fukui H, et al. Systematic review with meta-analysis: vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori. Helicobacter. 2018;23(4):e12495. https://doi.org/10.1111/hel.12495.

    Article  CAS  PubMed  Google Scholar 

  100. Tanabe H, Yoshino K, Ando K, Nomura Y, Ohta K, Satoh K, et al. Vonoprazan-based triple therapy is non-inferior to susceptibility-guided proton pump inhibitor-based triple therapy for helicobacter pylori eradication. Ann Clin Microbiol Antimicrob. 2018;17(1):29. https://doi.org/10.1186/s12941-018-0281-x.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Furuta T, Sahara S, Ichikawa H, Kagami T, Uotani T, Yamade M et al. Dual therapy with vonoprazan and amoxicillin is as effective as standard PPI-based triple therapy with amoxicillin and clarithromycin or metronidazole in Japan. Gastroenterology. 2016; 150(4). https://doi.org/10.1016/s0016-5085(16)32958-4.

    Google Scholar 

  102. • Graham DY, Dore MP. Update on the use of vonoprazan: a competitive acid blocker. Gastroenterology. 2018;154(3):462–6. https://doi.org/10.1053/j.gastro.2018.01.018 Thoughtful remarks on current and potential clinical use of vonoprazan.

    Article  PubMed  Google Scholar 

  103. Kim EH, Park CH. Vonoprazan-based Helicobacter pylori eradication therapy: time to get competitive? Dig Dis Sci. 2017;62(11):2955–7. https://doi.org/10.1007/s10620-017-4699-3.

    Article  PubMed  Google Scholar 

  104. Kawai T, Oda K, Funao N, Nishimura A, Matsumoto Y, Mizokami Y, et al. Vonoprazan prevents low-dose aspirin-associated ulcer recurrence: randomised phase 3 study. Gut. 2018;67(6):1033–41. https://doi.org/10.1136/gutjnl-2017-314852.

    Article  PubMed  Google Scholar 

  105. Mizokami Y, Oda K, Funao N, Nishimura A, Soen S, Kawai T, et al. Vonoprazan prevents ulcer recurrence during long-term NSAID therapy: randomised, lansoprazole-controlled non-inferiority and single-blind extension study. Gut. 2018;67(6):1042–51. https://doi.org/10.1136/gutjnl-2017-314010.

    Article  PubMed  Google Scholar 

  106. Leontiadis GI, Howden CW. The role of proton pump inhibitors in the management of upper gastrointestinal bleeding. Gastroenterol Clin N Am. 2009;38(2):199–213. https://doi.org/10.1016/j.gtc.2009.03.008.

    Article  Google Scholar 

  107. Greenspoon J, Barkun A. The pharmacological therapy of non-variceal upper gastrointestinal bleeding. Gastroenterol Clin N Am. 2010;39(3):419–32. https://doi.org/10.1016/j.gtc.2010.08.002.

    Article  Google Scholar 

  108. 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. https://doi.org/10.1124/jpet.117.244202.

    Article  CAS  PubMed  Google Scholar 

  109. Tajimi M, Nii T, Takahashi N, Yamamoto T, Koizumi S. First-in-human study of the novel acid pump antagonist, RQ-00000004, demonstrated a rapid elevation of gastric pH following single oral administration in healthy subjects. Gastroenterology. 2011; 140(5). doi:https://doi.org/10.1016/s0016-5085(11)60324-7.

    Article  Google Scholar 

  110. Han S, Choi HY, Kim YH, Nam JY, Song GS, Lim HS, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of escalating single and multiple Oral doses of CJ-12420 (tegoprazan), a novel potassium-competitive acid blocker (P-CAB) in healthy male subjects. Clin Ther. 2017;39(8):e97–e8. https://doi.org/10.1016/j.clinthera.2017.05.306.

    Article  Google Scholar 

  111. Lee C-H, Lee S-C, Lee Y-I,EOM D-K,Han RR, Koh EJ. Novel 4-methoxy pyrrole derivatives or salts thereof and pharmaceutical composition comprising the same. WO 2016/175555 A2.

  112. Sunwoo J, Oh J, Moon SJ, Ji SC, Lee SH, Yu KS, et al. Safety, tolerability, pharmacodynamics and pharmacokinetics of DWP14012, a novel potassium-competitive acid blocker, in healthy male subjects. Aliment Pharmacol Ther. 2018;48(2):206–18. https://doi.org/10.1111/apt.14818.

    Article  CAS  PubMed  Google Scholar 

  113. Unge P, Andersson K. A first-in-human, open-label, healthy volunteer study of the new P-CAB X842 demonstrating 24h acid control for treatment of acid related diseases. Gastroenterology. 2017;154(6, Suppl 1):S-238. https://doi.org/10.1016/S0016-5085(18)31174-0.

    Article  Google Scholar 

  114. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Ther Adv Gastroenterol. 2012;5(4):219–32. https://doi.org/10.1177/1756283x12437358.

    Article  Google Scholar 

  115. Cammarota S, Bruzzese D, Sarnelli G, Citarella A, Menditto E, Riegler S, et al. Proton pump inhibitors prescribing following the introduction of generic drugs. Eur J Clin Investig. 2012;42(10):1068–78. https://doi.org/10.1111/j.1365-2362.2012.02696.x.

    Article  Google Scholar 

  116. Gupta R, Garg P, Kottoor R, Munoz JC, Jamal MM, Lambiase LR, et al. Overuse of acid suppression therapy in hospitalized patients. South Med J. 2010;103(3):207–11. https://doi.org/10.1097/SMJ.0b013e3181ce0e7a.

    Article  PubMed  Google Scholar 

  117. Ahrens D, Chenot JF, Behrens G, Grimmsmann T, Kochen MM. Appropriateness of treatment recommendations for PPI in hospital discharge letters. Eur J Clin Pharmacol. 2010;66(12):1265–71. https://doi.org/10.1007/s00228-010-0871-9.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Parente F, Cucino C, Gallus S, Bargiggia S, Greco S, Pastore L, et al. Hospital use of acid-suppressive medications and its fall-out on prescribing in general practice: a 1-month survey. Aliment Pharmacol Ther. 2003;17(12):1503–6.

    Article  CAS  Google Scholar 

  119. Wermeling M, Himmel W, Behrens G, Ahrens D. Why do GPs continue inappropriate hospital prescriptions of proton pump inhibitors? A qualitative study. Eur J Gen Pract. 2014;20(3):174–80. https://doi.org/10.3109/13814788.2013.844787.

    Article  PubMed  Google Scholar 

  120. Johnell K, Klarin I. The relationship between number of drugs and potential drug-drug interactions in the elderly: a study of over 600,000 elderly patients from the Swedish prescribed drug register. Drug Saf. 2007;30(10):911–8.

    Article  Google Scholar 

  121. Marengoni A, Pasina L, Concoreggi C, Martini G, Brognoli F, Nobili A, et al. Understanding adverse drug reactions in older adults through drug-drug interactions. Eur J Intern Med. 2014;25(9):843–6. https://doi.org/10.1016/j.ejim.2014.10.001.

    Article  CAS  PubMed  Google Scholar 

  122. • Savarino V, Tosetti C, Benedetto E, Compare D, Nardone G. Appropriateness in prescribing PPIs: a position paper of the Italian Society of Gastroenterology (SIGE)—study section “digestive diseases in primary care”. Dig Liver Dis. 2018. https://doi.org/10.1016/j.dld.2018.07.004. Position paper of the Italian Society of Gastroenterology on PPI appropriateness.

    Article  Google Scholar 

  123. Thompson W, Hogel M, Li Y, Thavorn K, O'Donnell D, McCarthy L et al. Effect of a proton pump inhibitor deprescribing guideline on drug usage and costs in long-term care. J Am Med Dir Assoc. 2016; 17(7): 673 e1–4. https://doi.org/10.1016/j.jamda.2016.04.020.

    Article  Google Scholar 

  124. Hunt R, Sachs G. A review of the status of omeprazole: the Hambury workshop. Dig Dis Sci. 1995;40(2 Suppl):1s–131s.

    Article  CAS  Google Scholar 

  125. •• Vaezi MF, Yang YX, Howden CW. Complications of proton pump inhibitor therapy. Gastroenterology. 2017;153(1):35–48. https://doi.org/10.1053/j.gastro.2017.04.047 The most critical and detailed appraisal of the reported PPI adverse events, with main focus on biological plausibility and strength of association.

    Article  CAS  PubMed  Google Scholar 

  126. • Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706–15. https://doi.org/10.1053/j.gastro.2017.01.031 Best practice recommendations from the AGA on PPI use, taking into account benefits and risks.

    Article  CAS  Google Scholar 

  127. Kinoshita Y, Ishimura N, Ishihara S. Advantages and disadvantages of long-term proton pump inhibitor use. J Neurogastroenterol Motil. 2018;24(2):182–96. https://doi.org/10.5056/jnm18001.

    Article  PubMed  PubMed Central  Google Scholar 

  128. Savarino E, Marabotto E, Zentilin P, Furnari M, Bodini G, Pellegatta G, et al. A safety review of proton pump inhibitors to treat acid-related digestive diseases. Exp Opin Drug Saf. 2018;17(8):785–94. https://doi.org/10.1080/14740338.2018.1497155.

    Article  CAS  Google Scholar 

  129. •• Malfertheiner P, Kandulski A, Venerito M. Proton-pump inhibitors: understanding the complications and risks. Nature Rev Gastroenterol Hepatol. 2017;14(12):697–710. https://doi.org/10.1038/nrgastro.2017.117 Detailed review analyzing the level of evidence for the association between PPIs and the reported adverse events, with recommendations on management of some undesirable effects.

    Article  CAS  Google Scholar 

  130. Laine L, Nagar A. Long-term PPI use: balancing potential harms and documented benefits. Am J Gastroenterol. 2016;111(7):913–5. https://doi.org/10.1038/ajg.2016.156.

    Article  CAS  PubMed  Google Scholar 

  131. Yeomans ND, Dent J. Personal review: alarmism or legitimate concerns about long-term suppression of gastric acid secretion? Aliment Pharmacol Ther. 2000;14(3):267–71. https://doi.org/10.1046/j.1365-2036.2000.00750.x.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada

    Richard H. Hunt MB, FRCP, FRCP(C)

  2. Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy

    Carmelo Scarpignato MD, DSc, FRCP

Authors
  1. Richard H. Hunt MB, FRCP, FRCP(C)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carmelo Scarpignato MD, DSc, FRCP
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Both authors designed the flow chart and methodology of the paper. Each of them carried out an independent systematic search of the relevant literature using Medline/PubMed, Embase, and the Cochrane databases. Search outputs were discussed and distilled, paying more attention to systematic reviews and meta-analyses (where available). Each author then wrote given sections, amended by the other co-author. The final manuscript was then prepared, revised critically, and approved before its submission,

Corresponding author

Correspondence to Richard H. Hunt MB, FRCP, FRCP(C).

Ethics declarations

Conflict of Interest

Carmelo Scarpignato has served as a speaker, consultant and/or advisory board member for Alfasigma, Pfizer, Takeda, Reckitt-Benkiser and Shionogi, and has, in the past, received funding from Giuliani Pharmaceuticals and Pfizer. Richard H Hunt has served as a speaker, a consultant, and an advisory board member for AstraZeneca, Danone, GSK, Merck, Pfizer, and Takeda.

Human and Animal Rights and Informed Consent

This article does not contain (but only mention) any specific studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Stomach

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hunt, R.H., Scarpignato, C. Potent Acid Suppression with PPIs and P-CABs: What’s New?. Curr Treat Options Gastro 16, 570–590 (2018). https://doi.org/10.1007/s11938-018-0206-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11938-018-0206-y

Keywords

Search

Navigation