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Clinical Pharmacology of Omeprazole

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Summary

Omeprazole is a specific inhibitor of H+, K+-ATPase or ‘proton pump’ in parietal cells. This enzyme is responsible for the final step in the process of acid secretion; omeprazole blocks acid secretion in response to all stimuli. Single doses produce dose-dependent inhibition with increasing effect over the first few days, reaching a maximum after about 5 days. Doses of omeprazole 20mg daily or greater are able to virtually abolish intragastric acidity in most individuals, although lower doses have a much more variable effect. Omeprazole causes a dose-dependent increase in gastrin levels.

Omeprazole must be protected from intragastric acid when given orally, and is therefore administered as encapsulated enteric-coated granules. Absorption can be erratic but is generally rapid, and initially the drug is widely distributed. It is highly protein-bound and extensively metabolised. Its elimination half-life is about 1h but its pharmacological efTecl lasts much longer, since it is preferentially concentrated in parietal cells where it forms a covalent linkage with H+, K+-ATPase, which it irreversibly inhibits. Omeprazole binds to hepatic cytochrome P450 and inhibits oxidative metabolism of some drugs, the most important being Phenytoin.

Omeprazole has produced short term healing rates superior to the histamine H2-receptor antagonists in duodenal ulcer, gastric ulcer and reflux oesophagitis. It has also been shown to be highly effective in healing ulcers which have failed to respond to H2-receptor antagonists, and has been extremely valuable in treating patients with Zollinger-Ellison syndrome.

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References

  • Allen JM, Adrian TE, Webster J, Howe A, Bloom SR. Effecl of single dose of omeprazole on the gastrointestinal peptide response to food. Hepato-gastroenlerology 31: 44–46, 1984

    CAS  Google Scholar 

  • Andersson T, Cederberg C, Heggelund A, Lundborg P. Omeprazole pharmacokinetics of single and repeated once daily administration of 10, 20 and 40mg as enteric coated granules. Abstract. European Journal of Clinical Pharmacology 36 (Suppl.): AI42, 1989

    Google Scholar 

  • Archambault AP, Pare P, Bailey RJ, Navert H, Williams CN, et al. Omeprazole (20mg daily) versus Cimetidine (1200mg daily) in duodenal ulcer healing and pain relief. Gastroenterology 94: 1130–1134, 1988

    PubMed  CAS  Google Scholar 

  • Bardhan KD, Bianchi-Porro G, Bose K, Daly M, Hinchcliffe RFC, et al. A comparison of two different doses of omeprazole versus ranitidine in treatment of duodenal ulcer. Journal of Clinical Gastroenterology 8: 408–413, 1986

    Article  PubMed  CAS  Google Scholar 

  • Bardhan KD, Naesdal J, Bianchi-Porro G, Lazzaroni M, Hinchcliffe RFC, et al. Omeprazole in the treatment of refractory peptic ulcer. Abstract. Gastroenterology 94: A22, 1988

    Google Scholar 

  • Bate CM, Keeling PWN, O’Morain CA, Wilkinson SP, Mountford RA, et al. Omeprazole provides faster healing and symptom relief of reflux oesophagitis than Cimetidine. Abstract. Gut 302: A1493–A1494, 1989

    Google Scholar 

  • Blanchi A, Delchier J-C, Soule J-C, Payen D, Bader J-P. Control of acute Zollinger-Ellison syndrome with intravenous omeprazole. Lancet 2: 1223–1224, 1982

    Article  PubMed  CAS  Google Scholar 

  • Blum AL, Riecker EU, Dammann HG, Schiessel R, Lux G. et al. Comparison of omeprazole and ranitidine in the treatment of reflux esophagitis. New England Journal of Medicine 314: 716, 1986

    PubMed  CAS  Google Scholar 

  • Brunner G, Creutzfeldt W, Harke U, Lamberts R. Therapy with omeprazole in patients with peptic ulceration resistant to high-dose ranitidine treatment. Digestion 39: 80–90, 1988

    Article  PubMed  CAS  Google Scholar 

  • Cederberg C, Andersson T, Skanberg I. Omeprazole: pharmacokinetics and metabolism in man. Scandinavian Journal of Gastroenterology 24 (Suppl 166) 33–40, 1989

    Article  Google Scholar 

  • Ching MS, Mihaly GW, Angus PW, Morgan DJ, Devenish-Meares S, et al. Oral bioavailability of omeprazole before and after chronic therapy in duodenal ulcer patients. British Journal of Clinical Pharmacology, in press, 1990

  • Classen M, Dammann H-G, Domschke W, Huttemann W, Londong W, et al. Omeprazole heals duodenal, but not gastric, ulcers more rapidly than ranitidine. Hepato-gastroenterology 32: 243–245, 1985

    PubMed  CAS  Google Scholar 

  • Clissold SP, Campoli-Richard DM. Omeprazole: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome. Drugs 32: 15–47, 1986

    Article  PubMed  CAS  Google Scholar 

  • Danhof M, Soons PA, van den Berg G, van Brummelen P, Jansen JBMJ, et al. Interactions between nifedipine and omeprazole. Abstract. European Journal of Clinical Pharmacology 36 (Suppl.): A258, 1989

    Google Scholar 

  • Danish Omeprazole Study Group. Omeprazole and Cimetidine in the treatment of ulcers of the body of the stomach: double-blind comparative trial. British Medical Journal 298: 645–647, 1989

    Article  Google Scholar 

  • Dent J, Hetzel DJ, Mackinnon MA, Reed WD, Narielvala FM. Evaluation of omeprazole in reflux oesophagitis. Scandinavian Journal of Gastroenterology 24 (Suppl. 166): 76–82, 1989

    Article  Google Scholar 

  • Deviere J, Buset M, Dumonceau J-M, Rickaert F, Cremer M. Regression of Barrett’s epithelium with omeprazole. New England Journal of Medicine 320: 1497–1498, 1989

    Article  PubMed  CAS  Google Scholar 

  • Downton J, Dent J, Heddle R, et al. Elevation of gastric pH heals peptic oesophagitis — a role for omeprazole. Journal of Gastroenterology and Hepatology 2: 317–324, 1987

    Article  Google Scholar 

  • Festen HPM, Tuynman HARE, Defizc J, Frants RR, Straub JP, et al. Effect of single and repeated doses of oral omeprazole on gastric acid and pepsin secretion and fasting serum gastrin and serum pepsinogen I levels. Digestive Diseases and Sciences 31: 561–566, 1986

    Article  PubMed  CAS  Google Scholar 

  • Gugler R, Jensen JC. Omeprazole inhibits elimination of diazepam. Lancet 1: 96, 1984

    Google Scholar 

  • Gugler R, Jensen JC. Omeprazole inhibits oxidative drug metabolism: studies with diazepam and Phenytoin in vivo and 7-ethoxycoumarin in vitro. Gastroenterology 89: 1235–1241, 1985

    PubMed  CAS  Google Scholar 

  • Gustavsson S, Adami H-O, Loof L, Nyberg A, Nyren O. Rapid healing of duodenal ulcers with omeprazole: double-blind dosecomparative trial. Lancet 2: 124–125, 1983

    Article  PubMed  CAS  Google Scholar 

  • Havelund T, Laursen LS, Skoubo-Kristensen E, Andersen BN, Pedersen SA, et al. Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial. British Medical Journal 296: 89–92, 1988

    Article  PubMed  CAS  Google Scholar 

  • Henry DA, Somerville KW, Kitchingham G, Langman MJS. Omeprazole: effects on oxidative drug metabolism. British Journal of Clinical Pharmacology 18: 195–200, 1984

    Article  PubMed  CAS  Google Scholar 

  • Henry D, Brent P, Whyte I, Mihaly G. Devenish-Meares S, Propranolol steady-state pharmacokinetics arc unaltered by omeprazole. European Journal of Clinical Pharmacology 33: 369–373, 1987

    Article  PubMed  CAS  Google Scholar 

  • Hetzel DJ, Dent J, Reed WD, Narielvala FM, Mackinnon M, et al. Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology 95: 903–912, 1988

    PubMed  CAS  Google Scholar 

  • Howden CW, Beastall GH, Reid JL. An investigation into the effects of omeprazole on renal tubular function and endocrine function in man. Scandinavian Journal of Gastroenterology 21 (Suppl. 118): 169–170, 1986b

    Article  Google Scholar 

  • Howden CW, Derodra JK, Burget DW, Hunt RH. Effects of low dose omeprazole on gastric secretion and plasma gastrin in patients with healed duodenal ulcer. Hepato-gastroenterology 33: 267–270, 1986a

    PubMed  CAS  Google Scholar 

  • Howden CW, Forrest JAH, Meredith PA, Reid JL. Antisecretory effect and oral pharmacokinetics following low dose omeprazole in man. British Journal of Clinical Pharmacology 20: 137–139, 1985a

    Article  PubMed  CAS  Google Scholar 

  • Howden CW, Forrest JAH, Reid JL. Effects of single and repeated doses of omeprazole on gastric acid and pepsin secretion in man. Gut 25: 707–710, 1984a

    Article  PubMed  CAS  Google Scholar 

  • Howden CW, Hunt RH. The relationship between suppression of acidity and gastric ulcer healing rates. Alimentary Pharmacology and Therapeutics 4, in press. 1990

  • Howden CW, Kenyon CJ, Beastall GH, Reid JL. Inhibition by omeprazole of adrenocortical response to ACTH: clinical studies and experiments on bovine adrenal cortex in vitro. Clinical Science 70: 99–102, 1986c

    PubMed  CAS  Google Scholar 

  • Howden CW, Meredith PA, Forrest JAH, Reid JL. Oral pharmacokinetics of omeprazole. European Journal of Clinical Pharmacology 26: 641–643, 1984b

    Article  PubMed  CAS  Google Scholar 

  • Howden CW, Payton CD, Meredith PA, Hughes DMA, Macdougall AI, et al. Antisecretory cfTcci and oral pharmacokinetics of omeprazole in palients wiih chronic renal failure. European Journal of Clinical Pharmacology 28: 637–640, 1985b

    Article  PubMed  CAS  Google Scholar 

  • Howdcn CW, Reid JL. Omeprazole, a gaslric ‘proton pump mhihnor: lack of effect on renal handling of electrolytes and urinary acidification. European Journal of Clinical Pharmacology’ 26: 639–640, 1984

    Article  Google Scholar 

  • Howden CW, Reid JL. The effect of antacids and metoclopramide on omeprazole absorption and disposition. British Journal of Clinical Pharmacology 25: 779–781, 1988

    Article  PubMed  CAS  Google Scholar 

  • Jones DB, Howden CW, Burget DW, Kerr GD. Hunt RH Acid suppression in duodenal ulcer: a meta-analysis to define optimal dosing with antisecretory drugs. Gul 28: 1120–1127, 1987

    CAS  Google Scholar 

  • Klinkcnberg-Knol EC, Festen HPM, Meuwissen SGM. The effects of omeprazole and ranitidine on 24-hour pH in the distal oesophagus of patients with reflux oesophagitis. Alimentary Pharmacology and Therapeutics 2: 221–228, 1988

    Article  Google Scholar 

  • Klinkenbcrg-Knol EC, Jansen JBMJ, Festen HPM, Meuwissen SGM, Lamers CBHW. Doubleblind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis. Lancet 12: 349–351, 1987

    Article  Google Scholar 

  • 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 palients resistant to histamine H2-rcceptor antagonists. New England Journal of Medicine 310: 758–761, 1984

    Article  Google Scholar 

  • Lanzon-Miller S, Pounder RE, Hamilton MR, Ball S, Chronos NAF, et al. Twenty-four-hour intragastric acidity and plasma gastrin concentration before and during treatment with either ranitidine or omeprazole. Alimentary Pharmcology and Therapeutics I: 239–251, 1987

    Google Scholar 

  • Lind T, Andersson T, Skanberg I, Olbe L, Biliary excretion of [p14]-omeprazole in humans. Clinical Pharmacology and Therapeutics 42: 504–508, 1987

    Article  PubMed  CAS  Google Scholar 

  • Lind T, Cederberg C, Ekenved G, Haglund LI, Olbe L. Effect of omeprazole — a gaslric proton pump inhibitor — on penlagas-trin-stimulaled acid secretion in man. Gut 24: 270–276, 1983

    Article  PubMed  CAS  Google Scholar 

  • Lloyd-Davies KA, Rutgersson K, Solvell L. Omeprazole in the treatment of Zollinger-Ellison syndrome: a 4-year international study. Alimentary Pharmacology and Therapeutics 2: 13–32, 1988

    Article  PubMed  CAS  Google Scholar 

  • MacGilchrist AJ, Howdcn CW, Kenyon CJ, Beastall GH, Reid JL. The effects of omeprazole on endocrine function in man. European Journal of Clinical Pharmacology 32: 423–425, 1987

    Article  PubMed  CAS  Google Scholar 

  • McKee RF, MacGilchrist AJ, Garden OJ, Forrest JAH, Carter DC. The anti-secretory effect and pharmacokinetics of omeprazole in chronic liver disease. Alimentary Pharmacology and Therapeutics 2: 429–437, 1988

    Article  PubMed  CAS  Google Scholar 

  • Naesdal J, Andersson T, Bodemar G, Larsson R, RegÃ¥rdh C-G, et al. Pharmacokinetics of [14C]-omeprazole in patients with impaired renal fucntion. Clinical Pharmacology and Therapeutics 40: 344–351, 1986

    Article  PubMed  CAS  Google Scholar 

  • Naesdal J, Bankel M, Bodemar G, Gotthard R, Lundquisl G, et al. The effect of 20mg omeprazole daily on serum gastrin. 24-h intragastric acidity and bile acid concentration in duodenal ulcer patients. Scandinavian Journal of Gastroenterology 22: 5–12, 1987

    Article  PubMed  CAS  Google Scholar 

  • Öberg K, Lindstrom H. Reduction of gastric hypersecretion in Zollinger-Ellison syndrome with omeprazole. Lancet I: 66–67, 1983

    Article  Google Scholar 

  • Paulsen O, Hoglund P, Walder M. No effect of omeprazole-in-duced hypoacidity on the bioavailability of amoxycillin or ba-campicillin. Scandinavian Journal of Infectious Diseases 21: 219–223, 1989

    Article  PubMed  CAS  Google Scholar 

  • Prichard PJ, Walt RP, Kitchingman GK, Somerville KW, Langman MJS. Oral Phenytoin pharmacokinetics during omeprazole therapy. British Journal of Clinical Pharmacology 24: 543–545, 1987

    Article  PubMed  CAS  Google Scholar 

  • Prichard PJ, Yeomans ND, Mihaly GW, Jones DB, Buckle PJ. et al. Omeprazole: a study of its inhibition of gaslric pH and oral pharmacokinetics after morning or evening dosage. Gastroenterology 88: 64–69, 1985

    PubMed  CAS  Google Scholar 

  • Regardh C-G. Pharmacokinetics and metabolism of omeprazole in man. Scandinavian Journal of Gastroenterology 21 (Suppl. 1181): 99–104, 1986

    Article  Google Scholar 

  • Regardh C-G, Gabrielsson M, Hoffman K-J, Lofberg I, Skanberg I. Pharmacokinetics and metabolism of omeprazole in animals and man—an overview. Scandinavian Journal of Gastroenterology 21 (Suppl. 108): 79–94, 1985

    Article  Google Scholar 

  • Rondanelli R, Regazzi M, Cerutu R, Cisternino M, Sivelli R. et al. Pharmacokinetics of omeprazole in patients with liver disease. Abstract. European Journal of Clinical Pharmacology 36 (Suppl.): A56k, 1989

    Google Scholar 

  • Sachs G, Wallmark B. The gaslric H+, K+-ATPase: the site of action of omeprazole. Scandinavian Journal of Gastroenterology 24 (Suppl. 166): 3–11, 1989

    Article  Google Scholar 

  • Sharma BK, Santana I.A, Wood EC, Walt RP, Periera M. et al. Intragastric bacterial activity and nitrosation before, during and after treatment with omeprazole. British Medical Journal 289: 717–719, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sutfin T, Balmcr K, Boslrom H, Eriksson S, Hoglund P. et al. Stereoselective interaction of omeprazole with warfarin in healthy men. Therapeutic Drug Monitoring 11: 176–184, 1989

    Article  PubMed  CAS  Google Scholar 

  • Thompson JN, Barr J A, Collier N, Spencer J, Bush A. et al. Basal, sham fed and pentagastrin-stmulated gastric acid, pepsin and electrolytes after omeprazole 20mg and 40mg daily. Gut 26: 1018–1024, 1985

    Article  PubMed  CAS  Google Scholar 

  • Tuynman HARE, Festen HPM, Rohss K, Meuwissen SGM. Lack of effect of antacids on plasma concentrations of omeprazole given as enteric-coated granules. British Journal of Clinical Pharmacology 24: 833–835, 1987

    Article  PubMed  CAS  Google Scholar 

  • Tytgal GNJ, Lamers CBHW, Hameeteman W, Jansen JMBJ, Wilson JA. Omeprazole in peptic ulcers resistant to histamine H2-rcceptor antagonists. Alimentary Pharmacology and Therapeutics 1: 31–38, 1987

    Article  Google Scholar 

  • Utley RJ, Wright R, Beastall GH, Carter DC. The effect of omeprazole on insulin-induced gastric secretion in man. Scottish Medical Journal 30: 96–100, 1985

    PubMed  CAS  Google Scholar 

  • Vantrappen G, Rutgeerts L, Schurmans P, Coergrachts J-L. Omeprazole (40mg) is superior to ranitidine in short-term treatment of ulcerative reflux esophagilis. Digestive Diseases and Sciences 33: 523–529, 1988

    Article  PubMed  CAS  Google Scholar 

  • Walan A, Bader JP, Classen M, Lamers CBHW, Piper DW. et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. New England Journal of Medicine 320: 69–75, 1989

    Article  PubMed  CAS  Google Scholar 

  • Wallmark B. Omeprazole: mode of action and effect on acid secretion in animals. Scandinavian Journal of Gastroenterology 24 (Suppl. 166): 12–18, 1989

    Article  Google Scholar 

  • Walt RP, Gomes MdeFA, Wood EC, Logan LH, Pounder RE. Effect of daily oral omeprazole on 24 hour intragastric acidity. British Medical Journal 287: 12–14, 1983

    Article  PubMed  CAS  Google Scholar 

  • Wolfe MM, Soll AH. The physiology of gastric acid secretion. New England Journal of Medicine 319: 1707–1715, 1988

    Article  PubMed  CAS  Google Scholar 

  • Zeitoun P. Comparison of omeprazole with ranitidine in the treatment of reflux oesophagitis. Scandinavian Journal of Gastroenterology 24 (Suppl. 166): 83–87, 1989

    Article  Google Scholar 

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  1. University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, G11 6NT, Scotland

    Colin W. Howden

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Howden, C.W. Clinical Pharmacology of Omeprazole. Clin Pharmacokinet 20, 38–49 (1991). https://doi.org/10.2165/00003088-199120010-00003

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