Movatterモバイル変換

[0]ホーム
URL:

Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Advertisement

Nature Reviews Gastroenterology & Hepatology
  • Review Article
  • Published:

Insights into the future of gastric acid suppression

Nature Reviews Gastroenterology & Hepatologyvolume 6, pages524–532 (2009)Cite this article

Abstract

The development of effective acid-suppression therapy (particularly PPIs) has revolutionized the treatment of acid-related diseases. Despite the overall effectiveness of these agents, they have some shortcomings, including a delayed onset of action, incomplete acid suppression in the majority of patients, and the need for ingestion before a meal to achieve maximal efficacy. Attempts to overcome these issues have included the development of isomeric PPIs (such as esomeprazole), alterations in drug delivery (such as delayed-release dexlansoprazole), and combined therapy with nonenterically coated PPIs and antacids (such as 'naked' omeprazole combined with sodium biocarbonate). Other acid-suppression agents in development or in late-phase trials include potassium-competitive acid blockers, new histamine receptor 2 antagonists, and gastrin antagonists. Although these agents could potentially achieve complete gastric acid suppression, risks may be associated with this level of suppression, including enteric infections and malabsorption of nutrients such as vitamin B12, iron and calcium. This Review provides an update on the status of acid-suppression therapy and discusses directions for future research.

Key Points

  • Acid-suppression therapy can be improved to provide accelerated onset and prolonged duration of action, and avoid the need for timing of doses according to food intake

  • Isomeric PPIs, such as esomeprazole, have advantages over racemic mixtures for most (perhaps all) currently available agents

  • Delayed-release technologies, such as delayed-release dexlansoprazole, may improve the efficacy of PPI therapy

  • New agents with long half-lives, such as ilaprazole, tenatoprazole, potassium-competitive acid blockers, novel histamine receptor 2 antagonists, and gastrin antagonists, are under development and might have improved efficacy

  • Combining another agent, such as sodium bicarbonate, a histamine receptor 2 antagonist, cholecystokinin-receptor or gastrin-receptor antagonist, with a PPI may increase the efficacy of treatment

  • PPI therapy is generally safe; however, metabolic and infectious concerns and drug–drug interaction issues will need to be addressed as powerful agents with long durations of action are developed

This is a preview of subscription content,access via your institution

Access options

Access through your institution

Subscription info for Japanese customers

We have a dedicated website for our Japanese customers. Please go tonatureasia.com to subscribe to this journal.

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Parietal cells with proton pump activation and binding of PPIs to proton pumps.

Similar content being viewed by others

References

  1. Bell, N. J. & Hunt, R. H. Role of gastric acid suppression in the treatment of gastro-oesophageal reflux disease.Gut33, 118–124 (1992).

    CAS PubMed PubMed Central  Google Scholar 

  2. Shin, J. M. & Sachs, G. Pharmacology of proton pump inhibitors.Curr. Gastroenterol. Rep.10, 528–534 (2008).

    PubMed PubMed Central  Google Scholar 

  3. Nebel, O. T., Fornes, M. F. & Castell, D. O. Symptomatic gastroesophageal reflux: incidence and precipitating factors.Am. J. Dig. Dis.21, 953–956 (1976).

    CAS PubMed  Google Scholar 

  4. DeVault, K. R. & Castell, D. O. Guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Practice Parameters Committee of the American College of Gastroenterology.Arch. Intern. Med.155, 2165–2173 (1995).

    CAS PubMed  Google Scholar 

  5. Bell, N. J., Burget, D., Howden, C. W., Wilkinson, J. & Hunt, R. H. Appropriate acid suppression for the management of gastro-oesophageal reflux disease.Digestion51 (Suppl. 1), 59–67 (1992).

    PubMed  Google Scholar 

  6. Miner, P., Katz, P. O., Chen, Y. & Sostek, M. Gastric acid control with esomeprazole, lansoprazole, omeprazole, pantoprazole and rabeprazole: a five-way crossover study.Am. J. Gastroenterol.98, 2616–2620 (2003).

    CAS PubMed  Google Scholar 

  7. Johnson, D. A. et al. A comparison of esomeprazole and lansoprazole for control of intragastric pH in patients with symptoms of gastro-oesopahgeal reflux disease.Aliment. Pharmacol. Ther.22, 129–134 (2005).

    CAS PubMed  Google Scholar 

  8. Xue, S., Katz, P. O., Banerjee, P., Tutuian, R. & Castell, D. O. Bedtime H2 lockers improve nocturnal gastric acid control in GERD patients on proton pump inhibitors.Aliment. Pharmacol. Ther.15, 1351–1356 (2001).

    CAS PubMed  Google Scholar 

  9. Fackler, W. K., Ours, T. M., Vaezi, M. F. & Richter, J. E. Long-term effect of H2RA therapy on nocturnal gastric acid breakthrough.Gastroenterology122, 625–632 (2002).

    CAS PubMed  Google Scholar 

  10. Dean, B. B., Gano, A. D. Jr, Knight, K., Ofman, J. J. & Fass, R. Effectiveness of proton pump inhibitors in nonerosive reflux disease.Clin. Gastroenterol. Hepatol.2, 656–664 (2004).

    CAS PubMed  Google Scholar 

  11. Hatlebakk, J. G., Katz, P. O., Camacho-Lobato, L. & Castell, D. O. Proton pump inhibitors: better acid control when taken before a meal than without a meal.Aliment. Pharmacol. Ther.14, 1267–1272 (2000).

    CAS PubMed  Google Scholar 

  12. Hatlebakk, J. G., Katz, P. O., Kuo, B. & Castell, D. O. Nocturnal gastric acidity and acid breakthrough on different regimens of omeprazole 40 mg daily.Aliment. Pharmacol. Ther.12, 1235–1240 (1998).

    CAS PubMed  Google Scholar 

  13. 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.23, 1473–1477 (2006).

    CAS PubMed  Google Scholar 

  14. Yuan, Y. et al. The proportion of patients who are free of reflux symptoms during the initial days of treatment with proton pump inbitors (PPIs) in GERD trials: a meta-analysis [abstract].Gastroenterology134 (Suppl. 1), S174 (2008).

    Google Scholar 

  15. Hellström, P. M. & Vitols, S. The choice of proton pump inhibitor: does it matter?Basic Clin. Pharmacol. Toxicol.94, 106–111 (2004).

    PubMed  Google Scholar 

  16. Pantoflickova, D., Dorta, G., Ravic, M., Jornod, P. & Blum, A. L. Acid inhibition on the first day of dosing: comparison of four proton pump inhibitors.Aliment. Pharmacol. Ther.17, 1507–1514 (2003).

    CAS PubMed  Google Scholar 

  17. Erah, P. O., Goddard, A. F., Barrett, D. A., Shaw, P. N. & Spiller, R. C. The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment ofHelicobacter pylori infection.J. Antimicrob. Chemother.39, 5–12 (1997).

    CAS PubMed  Google Scholar 

  18. Gustavson, L. E. et al. Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state.Antimicrob. Agents Chemother.39, 2078–2083 (1995).

    CAS PubMed PubMed Central  Google Scholar 

  19. Debets-Ossenkopp, Y. J., Namavar, F. & MacLaren, D. M. Effect of an acidic environment on the susceptibility ofHelicobacter pylori to trospectomycin and other antimicrobial agents.Eur. J. Clin. Microbiol. Infect. Dis.14, 353–355 (1995).

    CAS PubMed  Google Scholar 

  20. Figura, N., Crabtree, J. E. & Dattilo, M.In vitro activity of lansoprazole againstHelicobacter pylori.J. Antimicrob. Chemother.39, 585–590 (1997).

    CAS PubMed  Google Scholar 

  21. Gatta, L. et al. Antimicrobial activity of esomeprazole versus omeprazole againstHelicobacter pylori.J. Antimicrob. Chemother.51, 439–442 (2003).

    CAS PubMed  Google Scholar 

  22. Laine, L. et al. Esomeprazole-basedHelicobacter pylori eradication therapy and the effect of antibiotic resistance: results of three US multicenter, double-blind trials.Am. J. Gastroenterol.95, 3393–3398 (2000).

    CAS PubMed  Google Scholar 

  23. Gisbert, J., Domínguez-Munoz, A., Domínguez-Martin, A., Gisbert, J. L. & Marcos, S. Esomeprazole-based therapy inHelicobacter pylori eradication: any effect by increasing the dose of esomeprazole or prolonging the treatment?Am. J. Gastroenterol.100, 1935–1940 (2005).

    CAS PubMed  Google Scholar 

  24. Rostom, A. et al. Prevention of NSAID-induced gastroduodenal ulcers.Cochrane Database of Systematic Reviews, Issue 4. Art. No. CD002296. doi: 10.1002/14651858.CD002296 (2002).

    Google Scholar 

  25. Yeomans, N. D. 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.N. Engl. J. Med.338, 719–726 (1998).

    CAS PubMed  Google Scholar 

  26. Yeomans, N. et al. An evidence-based analysis of esomeprazole therapy versus placebo for the prevention of gastric or duodenal ulcers in at-risk continuous NSAID users [Abstract].Gastroenterology126, A604 (2004).

    Google Scholar 

  27. Miner, P. B. et al. Pharmacokinetics of naproxen and esomeprazole in PN400, a single-tablet, multilayer formulation of enteric coated naproxen coupled with immediate-release esomeprazole [abstract].Gastroenterology136, T1972 (2009).

    Google Scholar 

  28. Niazi, M., Naucler, E. & Naesdal, J. A single capsule formulation of esomeprazole 40 mg and acetylsalicylic acid 325 mg compared with the monotherapies given separately: a single-dose bioequivalence study in healthy subjects [abstract].Gastroenterology136, W1021 (2009).

    Google Scholar 

  29. Andriulli, A. et al. High- versus low-dose proton pump inhibitors after endoscopic hemostasis in patients with peptic ulcer bleeding: a multicenter, randomized study.Am. J. Gastroenterol.103, 3011–3018 (2008).

    PubMed  Google Scholar 

  30. Hunt, R. H. Importance of pH control in the management of GERD.Arch. Intern. Med.159, 649–657 (1999).

    CAS PubMed  Google Scholar 

  31. Richter, J. E. et al. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis: a randomized controlled trial.Am. J. Gastroenterol.96, 656–665 (2001).

    CAS PubMed  Google Scholar 

  32. Scott, L. J., Dunn, C. J., Mallarkey, G. & Sharpe, M. Esomeprazole: a review of its use in the management of acid-related disorders.Drugs62, 1503–1538 (2002).

    CAS PubMed  Google Scholar 

  33. Castell, D. O. et al. Esomeprazole (40 mg) compared with lansoprazole (30 mg) in the treatment of erosive esophagitis.Am. J. Gastroenterol.97, 575–583 (2002).

    CAS PubMed  Google Scholar 

  34. Labenz, J. et al. A randomized comparitive study of esomeprazole 40 mg versus pantoprazole 40 mg for healing erosive oesophagitis: the EXPO study.Aliment. Pharmacol. Ther.21, 739–746 (2005).

    CAS PubMed  Google Scholar 

  35. Kim, K. A. et al. Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19.Clin. Pharmacol. Ther.72, 90–99 (2002).

    CAS PubMed  Google Scholar 

  36. Tanaka, M., Yamazaki, H., Hakusui, H., Nakamichi, N. & Sekino, H. Differential stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor, in extensive and poor metabolizers of pantoprazole: a preliminiary study.Chirality9, 17–21 (1997).

    CAS PubMed  Google Scholar 

  37. Mano, M. et al. Plasma direct injection high-performance liquid chromatographic method for simultaneously determining E3810 enantiomers and their metabolites by using flavoprotein-conjugated column.J. Pharm. Sci.85, 903–907 (1996).

    CAS PubMed  Google Scholar 

  38. Pai, V. G. et al. Comparative clinical trial ofS-pantoprazole versus racemic pantoprazole in the treatment of gastro-esophageal reflux disease.World J. Gastroenterol.12, 6017–6020 (2006).

    CAS PubMed PubMed Central  Google Scholar 

  39. Pai, V. & Pai, N. Randomized, double-blind, comparative study of dexrabeprazole 10 mg versus rabeprazole 20 mg in the treatment of gastroesophageal reflux disease.World J. Gastroenterol.13, 4100–4102 (2007).

    CAS PubMed PubMed Central  Google Scholar 

  40. Mansfield, P., Henry, D. & Tonkin, A. Single-enantiomer drugs: elegant science, disappointing effects.Clin. Pharmacokinet.43, 287–290 (2004).

    CAS PubMed  Google Scholar 

  41. Wu, J., Vakily, M., Witt, G. & Mulford, D. TAK-390MR vs. lansoprazole for maintenance of drug concentration above a threshold which corresponds to higher time at pH >4 [abstract].Am. J. Gastroenterol.102, S124 (2007).

    Google Scholar 

  42. Sharma, P. et al. TAK-390MR, a proton pump inhibitor (PPI) with a novel duel delayed release formulation is highly effective in the healing of erosive esophagitis: data from two randomized controlled trials [abstract].Gastroenterology134, S1073 (2008).

    Google Scholar 

  43. Lee, R. D., Vakily, M., Wu, J. & Atkinson, S. The effect and timing of food on the pharmacokinetics and pharmacodynamics of TAK-390MR (modified release): evidence for dosing flexibility [abstract].Am. J. Gastroenterol.102, S145 (2007).

    Google Scholar 

  44. Periclou, A. P. et al. A comparative pharmacodynamic study of IY-81149 versus omeprazole in patients with gastroesophageal reflux disease.Clin. Pharmacol. Ther.68, 304–311 (2000).

    CAS PubMed  Google Scholar 

  45. Galmiche, J. P. et al. Tentaprazole: a novel proton pump inhibitor with a prolonged plasma half-life: effects on intragastric pH and comparison with esomeprazole in healthy volunteers.Aliment. Pharmacol. Ther.19, 655–662 (2004).

    CAS PubMed  Google Scholar 

  46. Hunt, R. H. et al. Effect of intragastric pH of a PPI with a prolonged plasma half-life: comparison between tenatoprazole and esomeprazole on the duration of acid suppression in healthy male volunteers.Am. J. Gastroenterol.100, 1949–1956 (2005).

    CAS PubMed  Google Scholar 

  47. Thomson, A. B. et al. Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three-way crossover study.Aliment. Pharmacol. Ther.23, 1179–1187 (2006).

    CAS PubMed  Google Scholar 

  48. Shin, J. M. et al. Characterization of the inhibitory activity of tenatoparzole on the gastric H+,K+-ATPasein vitro andin vivo.Biochem. Pharmacol.71, 837–849 (2006).

    CAS PubMed  Google Scholar 

  49. Hunt, R. H. et al. Predictable, prolonged suppression of gastric acidity with a novel proton pump inhibitor, AGN 201904-Z.Aliment. Pharmacol. Ther.28, 187–197 (2008).

    CAS PubMed PubMed Central  Google Scholar 

  50. Castell, D. Review of immediate-release omeprazole for the treatment of gastric acid related disorders.Exp. Opin. Pharmacother.6, 2501–2510 (2005).

    CAS  Google Scholar 

  51. SantarusZegerid®(omeprazole/sodium bicarbonate) US full prescribing information [online], (2008).

  52. Castell, D., Bagin, R., Goldlust, B., Major, J. & Hepburn, B. Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal gastro-oesophageal reflux disease.Aliment. Pharmacol. Ther.21, 1467–1474 (2005).

    CAS PubMed  Google Scholar 

  53. Freston, J. W., Chiu, Y. L., Mulford, D. J. & Ballard, E. D. Comparative pharmacokinetics and safety of lansoprazole oral capsules and orally disintegrating tablets in healthy subjects.Aliment. Pharmacol. Ther.17, 361–367 (2003).

    CAS PubMed  Google Scholar 

  54. Fandriks, L., Lönroth, H., Pettersson, A. & Vakil, N. Can famotidine and omeprazole be combined on a once-daily basis?Scand. J. Gastroenterol.42, 689–694 (2007).

    PubMed  Google Scholar 

  55. Chowers, Y. et al. PPI activity is optimized by VB101, a parietal cell activator [abstract].Gastroenterology134, A172 (2008).

    Google Scholar 

  56. Andersson, K. & Carlsson, E. Potassium-competitive acid blockade: a new therapeutic strategy in acid-related diseases.Aliment. Pharmacol. Ther.108, 294–307 (2005).

    CAS  Google Scholar 

  57. Kahrilas, P. J. et al. A randomized, comparative trial of three doses of AZD0865 and esomeprazole for healing of reflux esophagitis.Clin. Gastroenterol. Hepatol.5, 1385–1391 (2007).

    CAS PubMed  Google Scholar 

  58. Dent, J. 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.103, 20–26 (2008).

    CAS PubMed  Google Scholar 

  59. MedicineNet.comfamotidine/calcium carbonate/magnesium hydroxide—chewable [online]

  60. Konturek, P. C. et al. Studies on the cytoprotective and antisecretory activity of ebrotidine: a review.Arzeimittelforschung47, 578–589 (1997).

    CAS  Google Scholar 

  61. Castillo, J. R., Torelló, J. & Hernandez, A. Liver injury caused by ebrotidine: a new example of the utility of the postmarketing surveillance.Eur. J. Clin. Pharmacol.56, 187–189 (2000).

    CAS PubMed  Google Scholar 

  62. Hirakawa, N. et al. A novel histamine 2 (H2) receptor antagonist with gastroprotective activity: II. Synthesis and pharmacological evaluation of 2-furfuryl-thio and 2-furfurylsulfinyl acetamide derivatives with heteroaromatic rings.Chem. Pharm. Bull. (Tokyo)46, 616–622 (1998).

    CAS  Google Scholar 

  63. Hersey, S. J. & Sachs, G. Gastric acid secretion.Physiol. Rev.75, 155–189 (1995).

    CAS PubMed  Google Scholar 

  64. Chen, D. et al. Altered control of gastric acid secretion in gastrin–cholecyctokinin double mutant mice.Gastroenterology126, 476–487 (2004).

    CAS PubMed  Google Scholar 

  65. Beltinger, J. et al. Effects of spiroglumide, a gastrin receptor antagonist, inhibits gastrin stimulated gastric acid secretion in humans [abstract].Gut54 (Suppl. VII), A36 (2005).

    Google Scholar 

  66. Dunlop, J. CCK receptor antagonists.Gen. Pharmacol.31, 519–524 (1998).

    CAS PubMed  Google Scholar 

  67. Scarpignato, C., Pelosini, I. & Di Mario, F. Acid suppression therapy: where do we go from here?Dig. Dis.24, 11–46 (2006).

    PubMed  Google Scholar 

  68. Iwase, K. et al. Regulation of growth of human gastric cancer by gastrin and glycine-extended progastrin.Gastroenterology113, 782–790 (1997).

    CAS PubMed  Google Scholar 

  69. Nishi, T., Makuuchi, H. & Weinstein, W. M. Changes in gastric ECL cells and parietal cells after long-term administration of high-dose omeprazole to patients with Barrett's esophagus.Tokai J. Exp. Clin. Med.30, 117–121 (2005).

    CAS PubMed  Google Scholar 

  70. Modlin, I. M., Lye, K. D. & Kidd, M. A 50-year analysis of 562 gastric carcinoids: small tumor or larger problem?Am. J. Gastroenterol.99, 23–32 (2004).

    PubMed  Google Scholar 

  71. Kuipers, E. J. et al. Atrophic gastritis andHelicobacter pylori infection in patients with reflux esophagitis treated with omeprazole or fundoplication.N. Engl. J. Med.334, 1018–1022 (1996).

    CAS PubMed  Google Scholar 

  72. Malfertheiner, P. et al. Current concepts in the management ofHelicobacter pylori infection: the Maastricht III consensus report.Gut56, 772–781 (2007).

    CAS PubMed  Google Scholar 

  73. Watson, S. A. & Smith, A. M. Hypergastrinemia promotes adenoma progression in the APCmin−/+ mouse model of familial adenomatous polyposis.Cancer Res.61, 625–631 (2001).

    CAS PubMed  Google Scholar 

  74. Yang, Y. X. et al. Chronic proton pump inhibitor therapy and the risk of colorectal cancer.Gastroenterology133, 748–754 (2007).

    CAS PubMed  Google Scholar 

  75. Chowdhury, J. R., Berkowitz, J. M., Praissman, M. & Fara, J. W. Effect of sulfated and non-sulfated gastrin and octapeptidecholecystokinin on cat gall bladderin vitro.Experientia32, 1173–1175 (1976).

    CAS PubMed  Google Scholar 

  76. Geevasinga, N., Coleman, P. L., Webster, A. C. & Roger, S. D. Proton pump inhibitors and acute interstitial nephritis.Clin. Gastroenterol. Hepatol.4, 597–604 (2006).

    CAS PubMed  Google Scholar 

  77. Laheij, R. J. F. et al. Risk of community-acquired pneumonia and use of gastric acid–suppressive drugs.JAMA292, 1955–1960 (2004).

    CAS PubMed  Google Scholar 

  78. Gulmez, S. E. et al. Use of proton pump inhibitors and the risk of community-acquired pneumonia: a population-based case–control study.Arch. Intern. Med.167, 950–955 (2007).

    CAS PubMed  Google Scholar 

  79. Dial, S., Delaney, J. A., Barkun, A. N. & Suissa, S. Use of gastric acid-suppressive agents and the risk of community-acquiredClostridium difficile-associated disease.JAMA294, 2989–2995 (2005).

    CAS PubMed  Google Scholar 

  80. Neal, R. K. et al. Recent treatment with H2 antagonists, antibiotics and gastric surgery as risk factors for salmonella infection [abstract].BMJ308, 176 (1994).

    CAS PubMed PubMed Central  Google Scholar 

  81. Neal, K. R., Scott, H. M., Slack, R. C. & Logan, R. F. Omeprazole as risk factor forCampylobacter gastroenteritis: case–control study.BMJ312, 414–415 (1996).

    CAS PubMed PubMed Central  Google Scholar 

  82. Cobelens, F. G., Leentvarr-Kuijpers, A., Kleijnen, J. & Coutinho, R. A. Incidence and risk factors of diarrhoea in Dutch travelers: consequences for priorities in pre-travel health advice.Trop. Med. Int. Health3, 896–903 (1998).

    CAS PubMed  Google Scholar 

  83. Yang, Y. X., Lewis, J. D., Epstein, S. & Metz, D. C. Long-term proton pump inhibitor therapy and risk of hip fracture.JAMA296, 2947–2953 (2006).

    CAS PubMed  Google Scholar 

  84. Recker, R. R. Calcium absorption and achlorhydria.N. Engl. J. Med.313, 70–73 (1985).

    CAS PubMed  Google Scholar 

  85. O'Connell, M. B. et al. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial.Am. J. Med.118, 778–781 (2005).

    CAS PubMed  Google Scholar 

  86. Marcuard, S. P., Albernaz, L. & Khazanie, P. G. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12).Ann. Intern. Med.120, 211–215 (1994).

    CAS PubMed  Google Scholar 

  87. Conrad, M. E. & Schade, S. G. Ascorbic acid chelates in iron absorption: a role for hydorcholoric acid and bile.Gastroenterology55, 35–45 (1968).

    CAS PubMed  Google Scholar 

  88. Koop, H. & Bachem, M. G. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy.J. Clin. Gastroenterol.14, 288–292 (1992).

    CAS PubMed  Google Scholar 

  89. US Food and Drug Administration.Update of Safety Review: Follow-up to the August 9, 2007, Communication about the Ongoing Safety Review of Omeprazole and Esomeprazole [online] (2007).

  90. Bhatt, D. L. et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents.J. Am. Coll. Cardiol.52, 1502–1517 (2008).

    PubMed  Google Scholar 

  91. Pezalla, E., Day, D. & Pulliadath, I. Initial assessment of clinical impact of a drug interaction between clopidogrel and proton pump inhibitors [letter].J. Am. Coll. Cardiol,52, 1038–1039 (2008).

    PubMed  Google Scholar 

  92. Ho, P. M. et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome.JAMA301, 937–944 (2009).

    CAS PubMed  Google Scholar 

  93. Juurlink, D. N. et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel.CMAJ180, 713–718 (2009).

    PubMed PubMed Central  Google Scholar 

  94. Simon, T. et al. Genetic determinants of response to clopidogrel and cardiovascular events.N. Engl. J. Med.360, 363–375 (2009).

    CAS PubMed  Google Scholar 

  95. Shaheen, N. J. The burden of gastrointestinal and liver diseases, 2006.Am. J. Gastroenterol.101, 2128–2138 (2006).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Mayo Clinic, FL, USA

    Kenneth R. DeVault & Nicholas J. Talley

Authors
  1. Kenneth R. DeVault
  2. Nicholas J. Talley

Corresponding author

Correspondence toKenneth R. DeVault.

Ethics declarations

Competing interests

K. R. DeVault is a Consultant for AstraZeneca and Takeda, and he receives financial support for research and education from Addex, AstraZeneca, Janssen and Takeda.

N. J. Talley is a Consultant for Astellas, AstraZeneca, Centocor, Eisai, Elsevier, Ferring, Focus Medical, Gilead, In2MedEd, Ironwood, McNeil Consumer, MedScape, Meritage, Metabolic, Microbia, Novartis, OptumHealth, Salix, SK Life Sciences, SteigerWald,The Journal of Medicine, Theravance and Wyeth. He receives financial support from Dynogen, GlaxoSmithKline and Tioga.

Rights and permissions

About this article

This article is cited by

Access through your institution
Buy or subscribe

Advertisement

Search

Advanced search

Quick links

Nature Briefing

Sign up for theNature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox.Sign up for Nature Briefing
[8]ページ先頭
©2009-2025 Movatter.jp