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Prospective study of efficacy and safety of lansoprazole in Zollinger-Ellison syndrome

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Abstract

Lansoprazole, a new substituted benzimidazole H+, K+-ATPase inhibitor, profoundly inhibits gastric acid secretion and has potential use in the management of diseases such as Zollinger-Ellison syndrome (ZES). In the present study we evaluated the efficacy and safety of lansoprazole in controlling acid hypersecretion in 20 patients with ZES. The starting dose was 60 mg once daily. Control of acid hypersecretion was defined as the dose required to reduce acid secretion to <10 meq/hr in the last hour before the next dose. Doses were adjusted upwards until effective control was achieved. Patients not controlled with 120 mg once daily were placed on twice daily lansoprazole. Most patients (90%) required lansoprazole once daily. During long-term follow-up (mean 18.5 months), 25% of patients required upward dose adjustments and 25% of patients required twice daily lansoprazole. Following cessation of therapy, the mean time for gastric acid output to reach half basal acid output was 39.1 hr. Lansoprazole was well-tolerated without side effects. Clinical chemistry and hematological studies were unchanged, and no gastric carcinoids developed. These results demonstrate that lansoprazole is a safe and effective inhibitor of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Because it has a long duration of action, lansoprazole can be used to control gastric acid hypersecretion in most patients with Zollinger-Ellison syndrome using a once daily dosing schedule.

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References

  1. Zollinger RM, Ellison EH: Primary peptic ulcerations of the jejunum associated with islet cell tumors of the pancreas. Ann Surg 142:709–728, 1955

    Google Scholar 

  2. Jensen RT, Maton PN: Zollinger-Ellison syndrome.In The Stomach. S Gustavsson, D Kumar, DY Graham (eds). London, Churchill Livingstone, 1991, pp 341–374

    Google Scholar 

  3. Collen MJ, Howard JM, McArthur KE, Raufman J-P, Cornelius MJ, Ciarleglio CA, Gardner JD, Jensen RT: Comparison of ranitidine and cimetidine in the treatment of gastric hypersecretion. Ann Intern Med 100:52–58, 1984

    Google Scholar 

  4. Jensen RT, Collen MJ, McArthur KE, Howard JM, Maton PN, Cherner JA, Gardner JD: Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states. Am J Med 77:90–105, 1984

    Google Scholar 

  5. Howard JM, Chremos AN, Collen MJ, McArthur KE, Cherner JA, Maton PN, Ciarleglio CA, Cornelius MJ, Gardner JD, Jensen RT: Famotidine, a new, potent, long-acting histamine H2-receptor antagonist: Comparison with cimetidine and ranitidine in the treatment of Zollinger-Ellison syndrome. Gastroenterology 88:1026–1033, 1985

    Google Scholar 

  6. Vinayek R, Howard JM, Maton PN, Wank SA, Slaff JL, Gardner JD, Jensen RT: Famotidine in the therapy of gastric hypersecretory states. Am J Med 81 (suppl 4B):49–59, 1986

    Google Scholar 

  7. Maton PN, Gardner JD, Jensen RT: Recent advances in the management of gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. Gastroenterol Clin North Am 18:847–863, 1989

    Google Scholar 

  8. Jensen RT, Doppman JL, Gardner JD: Gastrinoma.In The Exocrine Pancreas: Biology, Pathobiology, and Diseases. VLW Go, JD Gardner, FP Brooks, E Lebenthal, EP Dimagno, G Scheele (eds). New York, Raven Press, 1986, pp 727–745

    Google Scholar 

  9. Jensen RT, Gardner JD, Raufman JP, Pandol SJ, Doppman JL, Collen MJ: Zollinger-Ellison syndrome. NIH Combined Clinical Staff Conference. RT Jensen (moderator). Ann Intern Med 98:59–75, 1983

    Google Scholar 

  10. Jensen RT: Basis for failure of cimetidine in patients with Zollinger-Ellison syndrome. Dig Dis Sci 29:363–366, 1984

    Google Scholar 

  11. McCarthy DM: Report on the United States experience with cimetidine in Zollinger-Ellison syndrome and other hypersecretory states. Gastroenterology 74:453–458, 1978

    Google Scholar 

  12. McCarthy DM, Hyman PE: Effect of isopropamide on response to oral cimetidine in patients with Zollinger-Ellison syndrome. Dig Dis Sci 27:353–359, 1982

    Google Scholar 

  13. Richardson CT, Walsh JH: The value of histamine H2-receptor antagonists in management of patients with Zollinger-Ellison syndrome. N Engl J Med 294:131–135, 1976

    Google Scholar 

  14. Maton PN, Frucht H, Vinayek R, Wank SA, Gardner JD, Jensen RT: Medical management of patients with Zollinger-Ellison syndrome who have had previous gastric surgery: A prospective study. Gastroenterology 94:294–299, 1988

    Google Scholar 

  15. Miller LS, Vinayek H, Frucht H, Gardner JD, Jensen RT, Maton PN: Reflux esophagitis in patients with Zollinger-Ellison syndrome. Gastroenterology 98:341–346, 1990

    Google Scholar 

  16. Jensen RT, Gardner JD: Zollinger-Ellison syndrome. Clinical presentation, pathology, diagnosis and treatment.In Peptic Ulcer and Other Acid-Related Diseases. A Dannenberg, D Zakim (eds). New York, Academic Research Assoc., 1991, pp 117–212

    Google Scholar 

  17. Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjostrand SE, Wallmark B: Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+/K+) ATPase. Nature 290:159–161, 1981

    Google Scholar 

  18. Clissold SP, Campoli-Richards DM: Omeprazole. Drugs 32:15–47, 1986

    Google Scholar 

  19. Frucht H, Maton PN, Jensen RT: Use of omeprazole in patients with Zollinger-Ellison syndrome. Dig Dis Sci 36:394–404, 1991

    Google Scholar 

  20. Lamers CBHW, Lind T, Moberg S, Jansen JBMJ, Olbe L: Omeprazole in Zollinger-Ellison syndrome. Effects of a single dose and of long-term treatment in patients resistant to histamine H2-receptor antagonists. N Engl J Med 310:758–761, 1984

    Google Scholar 

  21. Lloyd-Davies KA, Rutgersson K, Solvell L: Omeprazole in the treatment of Zollinger-Ellison syndrome: A 4-year international study. Aliment Pharmacol Ther 2:13–32, 1988

    Google Scholar 

  22. Maton PN, Vinayek R, Frucht H, McArthur KA, Miller LS, Saeed ZA, Gardner JD, Jensen RT: Long-term efficacy and safety of omeprazole in patients with Zollinger-Ellison syndrome: A prospective study. Gastroenterology 97:827–836, 1989

    Google Scholar 

  23. Hirschowitz BI, Deren J, Raufman JP, LaMont B, Berman R, Humphries T: A multicenter US study of omeprazole treatment of Zollinger-Ellison syndrome (ZES). Gastroenterology 94:A188, 1988

    Google Scholar 

  24. McArthur KE, Collen MJ, Maton PN, Cherner JA, Howard JM, Ciarleglio CA, Cornelius MJ, Jensen RT, Gardner JD: Omeprazole: Effective, convenient therapy for Zollinger-Ellison syndrome. Gastroenterology 88:939–944, 1985

    Google Scholar 

  25. Lehy T, Mignon M, Cadiot G, Elouaer-Blanc L, Ruszniewski P, Levin MJM, Bonfils S: Gastric endocrine cell behavior in Zollinger-Ellison patients upon long-term antisecretory treatment. Gastroenterology 96:1029–1040, 1989

    Google Scholar 

  26. Blanchi A, Delchier JC, Soule JC, Payen D, Bader JP: Control of acute Zollinger-Ellison syndrome with intravenous omeprazole. Lancet 2:1223–1224, 1982

    Google Scholar 

  27. Oberg K, Lindstrom H: Reduction of gastric hypersecretion in Zollinger-Ellison syndrome with omeprazole. Lancet 1:66–67, 1983

    Google Scholar 

  28. Vezzadini P, Tomassetti P, Toni R, Bonora G, Labo G: Omeprazole in the medical treatment of Zollinger-Ellison syndrome. Curr Ther Res 35:772–776, 1984

    Google Scholar 

  29. Delchier JC, Soule JC, Mignon M, Goldfain D, Cortot A, Travers B, Isal JP, Bader JP: Effectiveness of omeprazole in seven patients with Zollinger-Ellison syndrome resistant to histamine H2-receptor antagonists. Dig Dis Sci 31:693–699, 1986

    Google Scholar 

  30. Bardram L, Stadil F: Omeprazole in the Zollinger-Ellison syndrome. Scand J Gastroenterol 21:374–378, 1986

    Google Scholar 

  31. Corleto J, Puoti M, Annibale B, Saggioro A, D'Ambra G, DiPaola M, Della Fave G: Loss of efficacy of famotidine (FMT) in the control of gastric acid secretion in patients with Zollinger-Ellison syndrome (ZES) reversed by omeprazole (OMP). Gastroenterology 94:A79, 1988

    Google Scholar 

  32. Vezzadini P, Tomassetti P, Marrano D, Labo G: Life threatening gastrointestinal hemorrhage with omeprazole. Dig Dis Sci 33:766–767, 1988

    Google Scholar 

  33. Vinayek R, Frucht H, London JF, Miller LS, Stark HA, Norton JA, Cederberg C, Jensen RT, Gardner JD, Maton PN: Intravenous omeprazole in patients with Zollinger-Ellison syndrome undergoing surgery. Gastroenterology 99:10–16, 1990

    Google Scholar 

  34. Vinayek R, Amantea MA, Maton PN, Frucht H, Gardner JD, Jensen RT: Pharmacokinetics of oral and intravenous omeprazole in patients with Zollinger-Ellison syndrome. Gastroenterology 101:138–147, 1991

    Google Scholar 

  35. Kubo K, Oda K, Kaneko T, Satoh H, Nohara A: Synthesis of 2-{[(4-fluoroalkoxy-2-pyridyl)methyl]sulfinyl}-1H-benzimidazoles as antiulcer agents. Chem Pharm Bull (Tokyo) 38:2853–2858, 1990

    Google Scholar 

  36. Iwahi T, Satoh H, Nakao M, Iwasaki T, Yamazaki T, Kubo K, Tamura T, Imada A: Lansoprazole, a novel benzimidazole proton pump inhibitor, and its related compounds have selective activity against helicobacter pylori. Antimicrobiol Agents Chemother 35:490–496, 1991

    Google Scholar 

  37. Satoh H, Inatomi N, Nagaya H, Inada I, Nohara A, Maki Y: Antisecretory activity of AG1749, a proton pump inhibitor. Jpn J Pharmacol 40(suppl):226P, 1986

    Google Scholar 

  38. Satoh H, Inatomi N, Nagaya H, Inada I, Nohara A, Nakamura N, Maki Y: Antisecretory and antiulcer activities of a novel proton pump inhibitor AG-1749 in dogs and rats. J Pharmacol Exp Ther 248:806–815, 1989

    Google Scholar 

  39. Nagaya H, Satoh H, Maki Y: Possible mechanism for the inhibition of acid formation by the proton pump inhibitor AG 1749 in isolated canine parietal cells. J Pharmacol Exper Ther 252:1289–1295, 1990

    Google Scholar 

  40. Inatomi N, Satoh H, Nagaya H, Inada I, Sino A, Maki Y: Antiulcer activity of AG-1749, a proton pump inhibitor. Jpn J Pharmacol 43(suppl):233P, 1987

    Google Scholar 

  41. Müller P, Dammann HG, Leucht U, Simon B: Human gastric acid secretion following repeated doses of AG-1749. Aliment Pharmacol Ther 3:193–198, 1989

    Google Scholar 

  42. Dammann HG, Simon B, Müller P: 24 hour intragastric acidity under AG 1749—a newly developed proton pump inhibitor. Gastroenterology 96:A108, 1989

    Google Scholar 

  43. Sanders SW, Tolman KG, Sikora PA, Jennings DE, Hoyos PA, Page JG: Comparison of gastric pH following multiple oral AM and PM dosing of a new H+, K+-ATPase inhibitor, further evidence for diurnal variation in gastric acid secretion. Pharmacotherapy 8:141, 1988

    Google Scholar 

  44. Kihara K, Yoshida Y, Hirose M, Kasano T, Sato Y, Kimura K: A study of the inhibition of gastric pH after the morning and evening administration of AG 1749. Nissho Shi 85:2693, 1988 (in Japanese)

    Google Scholar 

  45. Hawkey CJ, Bardhan KD, Long RG, Wormsley KG, Cochran RM, Christian J, Moules I: Improved symptom relief and duodenal ulcer healing with lansoprazole compared to ranitidine. Gastroenterology 100:A80, 1991

    Google Scholar 

  46. Robinson MG, Campbell DR, Sontag S, Sabesin SM, Greski PA, Jennings DE, Guy JM: Lansoprazole heals H2 resistant erosive reflux esophagitis. Gastroenterology 98:A113, 1990

    Google Scholar 

  47. Stanescu L, Soule J-C, Robaskiewicz M, Goveroo H, Lemaire M: Effect of lansoprazole (L) and ranitidine (R) on esophageal acid over 24 hour periods in patients with symptomatic esophagitis. Gastroenterol Clin Biol 14:A108, 1990

    Google Scholar 

  48. Petite JP, Salducci J, Evreux M, Lemaire M: Lansoprazole (L) vs ranitidine (R) in the treatment of peptic esophagitis. Gastroenterol Clin Biol 14:A108, 1990

    Google Scholar 

  49. Antonson CW, Robinson MG, Hawkins TM, McIntosh DL, Campbell DR: High doses of histamine antagonists do not prevent relapses of peptic esophagitis following therapy with a proton pump inhibitor. Gastroenterology 98:A16, 1990

    Google Scholar 

  50. Bardhan KD, Long R, Hawkey CJ, Wormsley KG, Brocklebank D, Moules I: Lansoprazole, a new proton pump blocker, vs ranitidine in the treatment of reflux erosive esophagitis. Gastroenterology 100:A30, 1991

    Google Scholar 

  51. Sharma HK, Daneshmend TK, Hawthorne AB, Bhaskar NK, Hawkey CJ: Human gastric mucosal protection by AG 1749, a new potent proton pump inhibitor. Gastroenterology 96:A464, 1989

    Google Scholar 

  52. Bigard MA, Joubert M, DeMeynard C: Complete prevention by lansoprazole of aspirin induced gastric lesions in healthy subjects. Gastroenterology 100:A34, 1991

    Google Scholar 

  53. Hochlaf S, Vatier J, Ruszniewski CH, Poiterin MJM, Mignon M: Is lansoprazole as effective as omeprazole in patients with Zollinger-Ellison syndrome (ZES)? Gastroenterology 100:A24, 1991

    Google Scholar 

  54. Frucht H, Howard JM, Slaff JI, McCarthy DM, Maton PN, Wank SA, Vinayek R, Gardner JD, Jensen RT: Secretin and calcium provocative tests in Zollinger-Ellison syndrome. Ann Intern Med 111:713–722, 1989

    Google Scholar 

  55. Raufman J-P, Collins SM, Pandol SJ, Korman LY, Collen MJ, Cornelius MJ, Feld MK, McCarthy DM, Gardner JD, Jensen RT: Reliability of symptoms in assessing control of gastric acid secretion in patients with Zollinger-Ellison syndrome. Gastroenterology 84:108–113, 1983

    Google Scholar 

  56. London JF, Shawker TH, Doppman JL, Miller DL, Frucht H, Vinayek R, Stark HA, Miller LS, Norton JA, Jensen RT, Gardner JD, Maton PN: Prospective assessment of abdominal ultrasound in patients with Zollinger-Ellison syndrome. Radiology 178:763–767, 1991

    Google Scholar 

  57. Wank SA, Doppman JL, Miller DL, Collen MJ, Maton PN, Vinayek R, Norton JA, Gardner JD, Jensen RT: Prospective study of the ability of computerized axial tomography to localize gastrinomas in patients with Zollinger-Ellison syndrome. Gastroenterology 92:905–912, 1987

    Google Scholar 

  58. Frucht H, Doppman JL, Norton JA, Miller DL, Dwyer AJ, Frank JA, Vinayek R, Maton PN, Jensen RT: Gastrinomas: Comparison of MR imaging with CT, angiography and US. Radiology 171:713–717, 1989

    Google Scholar 

  59. Doppman JL, Miller DL, Chang R, Maton PN, London JF, Frucht H, Gardner JD, Jensen RT, Norton JA: Gastrinomas: Localization by means of selective intraarterial injection of secretin. Radiology 174:25–29, 1990

    Google Scholar 

  60. Lanzon-Miller S, Pounder RE, Hamilton MR, Ball S, Chronos NAF, Olausson FRM, Cederberg C: Twenty-four hour intragastric acidity and plasma gastrin concentrations before and during treatment with either ranitidine or omeprazole. Aliment Pharmacol Ther 1:239–251, 1987

    Google Scholar 

  61. Valenzuela JE, Berlin RG, Snape WJ, Johnson TL, Hirschowitz BI, Colon-Pagan J, Morse RS, Petrozza J, Van Deventer GM, Cagliola A, Whipple J, Berman R, Humphries TJ, and the Omeprazole DU Comparative Study Group: US experience with omeprazole in duodenal ulcer—multicenter double-blind comparative study with ranitidine. Dig Dis Sci 36:761–768, 1991

    Google Scholar 

  62. Maton PN, Lack EE, Collen MJ, Cornelius MJ, David E, Gardner JD, Jensen RT: The effect of Zollinger-Ellison syndrome and omeprazole therapy on gastric oxyntic endocrine cells. Gastroenterology 99:943–950, 1990

    Google Scholar 

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Author notes

  1. Paul N. Maton MD

    Present address: Oklahoma Center for Digestive Medicine, Oklahoma City, Oklahoma

  2. Jerry D. Gardner MD

    Present address: Department of Internal Medicine, St. Louis University Medical Center, St. Louis, Missouri

Authors and Affiliations

  1. Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10 Room 9C-103, 20892, Bethesda, Maryland

    David C. Metz MD, Joseph R. Pisegna MD, Gary L. Ringham PhD, Kathryn Feigenbaum CGRN, Pamela D. Koviack CGRN,  Paul N. Maton MD,  Jerry D. Gardner MD & Robert T. Jensen MD

  2. TAP Pharmaceutical Inc., Deerfield, Illinois

    Robert T. Jensen MD

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  1. David C. Metz MD
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Metz, D.C., Pisegna, J.R., Ringham, G.L. et al. Prospective study of efficacy and safety of lansoprazole in Zollinger-Ellison syndrome. Digest Dis Sci 38, 245–256 (1993). https://doi.org/10.1007/BF01307541

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