Skip to main content
Log in

Lack of effect of omeprazole treatment on steady-state plasma levels of metoprolol

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

In a randomised double-blind crossover study, seven healthy males were concomitantly given metoprolol 100 mg o. d. as a controlled release formulation, and omeprazole 40 mg o. d. or placebo, for 8 days. Plasma levels of the R- and S-enantiomers of metoprolol were determined on the 8th day of each treatment. The subjects were also characterised by their metabolic capacity to hydroxylate debrisoquine. Concomitant omeprazole treatment had no significant influence on the steady-state plasma levels of the two enantiomers of metoprolol. All subjects were characterised by extensive debrisoquine hydroxylation, i.e. extensive metoprolol metabolism.

As metoprolol is metabolised to a great extent by debrisoquine hydroxylase (IID6), it is concluded that concomitant omeprazole treatment will probably have a negligible influence on the metabolism of the relatively large number of drugs mainly metabolised by this isoenzyme of the cytochrome P450 family.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

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

    Google Scholar 

  2. Wallmark B, Lorentzon P, Larsson H (1985) The mechanism of action of omeprazole — a survey of its inhibitory actions in vitro. Scand J Gastroenterol 20 [Suppl 108]: 37–51

    Google Scholar 

  3. Lind T, Cederberg C, Ekenved G, Haglund U, Olbe L (1983) Effect of omeprazole — a gastric proton pump inhibitor — on pentagastrin stimulated acid secretion in man. Gut 24: 270–276

    Google Scholar 

  4. Wallmark B, Brändström A, Larsson H (1984) Evidence for acid-induced transformation of omeprazole into an active inhibitor of (H+, K+)-ATPase within the parietal cell. Biochim Biophys Acta 778: 549–558

    Google Scholar 

  5. Bardhan KD, Bianchi Porro G, Bose K, Daly M, Hinchliffe RFC, Jonsson E, Lazzaroni M, Naesdal J, Rikner L, Walan A (1986) A comparison of two different doses of omeprazole versus ranitidine in treatment of duodenal ulcer. J Clin Gastroenterol 8: 408–413

    Google Scholar 

  6. Hetzel DJ, Dent J, Reed WD, Narielvala FM, Mackinnon M, McCarthy JH, Mitchell B, Beveridge BR, Laurence BH, Gibson GG, Grant AK, Shearman DJC, Whitehead R, Buckle PJ (1988) Healing and relapse of severe peptic esophagitis after treatment with omeprazole. Gastroenterology 95: 903–912

    Google Scholar 

  7. Klinkenberg-Knol EC, Jansen JMBJ, Festen HPM, Meuwissen SGM, Lamers CBHW (1987) Double-blind multicentre comparison of omeprazole and ranitidine in the treatment of reflux oesophagitis. Lancet I: 349–351

    Google Scholar 

  8. Walan A, Bader JP, Classen M, Lamers CBHW, Piper DW, Rutgersson K, Eriksson S (1989) Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med 320: 69–75

    Google Scholar 

  9. Dickins M, Bridges JW (1982) The relationship between the binding of 2-n-alkylbenzimidazoles to rat hepatic microsomal cytochrome P450 and the inhibition of monooxygenation. Biochem Pharmacol 31: 1315–1320

    Google Scholar 

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

    Google Scholar 

  11. Andersson T, Andrén K, Cederberg C, Edvardsson G, Heggelund A, Lundborg P (1990) Effect of omeprazole and cimetidine on diazepam plasma levels. Eur J Clin Pharmacol 39: 51–54

    Google Scholar 

  12. Andersson T, Cederberg C, Edvardsson G, Heggelund A, Lundborg P (1990) Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. Clin Pharmacol Ther 47: 79–85

    Google Scholar 

  13. Sutfin T, Balmér K, Boström H, Eriksson S, Höglund P, Paulsen O (1989) Stereoselective interaction of omeprazole with warfarin in healthy men. Ther Drug Monit 11: 176–184

    Google Scholar 

  14. Andersson T, Lagerström PO, Unge P (1990). A study of the interaction between omeprazole and phenytoin in epileptic patients. Ther Drug Monit 12: 329–333

    Google Scholar 

  15. Gugler R, Jensen JC (1987) Drugs other than H2-receptor antagonists as clinically important inhibitors of drug metabolism in vivo. Pharmacol Ther 33: 133–137

    Google Scholar 

  16. Henry D, Brent P, Whyte I, Mihaly G, Devenish-Meares S (1987) Propranolol steady-state pharmacokinetics are unaltered by omeprazole. Eur J Clin Pharmacol 33: 369–373

    Google Scholar 

  17. Lennard MS, Silas JH, Freestone S, Ramsay LE, Tucker GT, Woods HF (1982) Oxidation phenotype — a major determinant of metoprolol metabolism and response. N Engl J Med 307: 1558–1560

    Google Scholar 

  18. Lennard MS, Silas JH, Freestone S, Trevethick J (1982) Defective metabolism of metoprolol in poor hydroxylators of debrisoquine. Br J Clin Pharmacol 14: 301–303

    Google Scholar 

  19. Lennard MS, Silas JH, Smith AJ, Tucker GT (1977) Determination of debrisoquine and its 4-hydroxy metabolite in biological fluids by gas chromatography with flame-ionization and nitrogen-selective detection. J Chromatogr 133: 161–166

    Google Scholar 

  20. Persson BA, Balmér K, Lagerström PO (1990) Enantioselective determination of metoprolol in plasma by liquid chromatography on a silica-bonded α1-acid glycoprotein column. J Chromatogr 500: 629–636

    Google Scholar 

  21. Brøsen K, Gram LF (1989) Clinical significance of the sparteine/debrisoquine oxidation polymorphism. Eur J Clin Pharmacol 36: 537–547

    Google Scholar 

  22. Andersson T, Reg»rdh CG, Dahl-Puustinen ML, Bertilsson L (1990) Slow omeprazole metabolisers are also poor S-mephenytoin hydroxylators. Ther Drug Monit 12: 415–416

    Google Scholar 

  23. Borg KO, Carlsson E, Hoffmann KJ, Jönsson TE, Thorin H, Wallin B (1975) Metabolism of metoprolol (-3H) in man, the dog and the rat. Acta Pharmacol Toxicol 36 [Suppl V]: 125–135

    Google Scholar 

  24. Gonzales FJ (1989) The molecular biology of cytochrome P450s. Pharmacol Rev 40: 243–288

    Google Scholar 

  25. Lennard MS, Tucker GT, Silas JH, Freestone S, Ramsay LE, Woods HF (1983) Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquine metabolisers. Clin Pharmacol Ther 34: 732–737

    Google Scholar 

  26. Drøhse A, Bathum L, Brösen K, Gram LF (1989) Mephenytoin and sparteine oxidation: genetic polymorphisms in Denmark. Br J Clin Pharmacol 27: 620–625

    Google Scholar 

  27. Guengerich FP, Müller-Enoch D, Blair IA (1986) Oxidation of quinidine by human liver cytochrome P-450. Molec Pharmacol 30: 287–295

    Google Scholar 

  28. Leemann T, Dayer P, Meyer UA (1986) Single-dose quinidine treatment inhibits metoprolol oxidation in extensive metabolisers. Eur J Clin Pharmacol 29: 739–741

    Google Scholar 

  29. Ward SA, Walle T, Walle UK, Wilkinson GR, Branch RA (1989) Propranolol's metabolism is determined by both mephenytoin and debrisoquine hydroxylase activities. Clin Pharmacol Ther 45: 72–79

    Google Scholar 

  30. Robson RA, Miners JO, Matthews AP, Stupans I, Meller D, McManus ME, Birkett DJ (1988) Characterisation of theophylline metabolism by human liver microsomes. Biochem Pharmacol 37: 1651–1659

    Google Scholar 

  31. Bertilsson L, Henthorn TK, Sanz E, Tybring G, Säwe J, Willén T (1989) Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquine, hydroxylation phenotype. Clin Pharmacol Ther 45: 348–355

    Google Scholar 

  32. Advances In Therapy (1988) 5: 153–272

  33. Rendić S, Kajfež F, Ruf HH (1983) Characterisation of cimetidine, ranitidine, and related structures' interaction with cytochrome P450, Drug Metab Dispos 11: 137–142

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andersson, T., Lundborg, P. & Reg»rdh, C.G. Lack of effect of omeprazole treatment on steady-state plasma levels of metoprolol. Eur J Clin Pharmacol 40, 61–65 (1991). https://doi.org/10.1007/BF00315140

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00315140

Key words

Navigation