Summary
The effects of steady state dosing with omeprazole and cimetidine on plasma diazepam levels have been studied in 12 healthy males. Single doses of diazepam (0.1 mg · kg−1 i.v.) were administered after one week of treatment with omeprazole 20 mg once daily, cimetidine 400 mg b. d. or placebo, and the treatment was continued for a further 5 days. Blood was collected for 120 h after the dose of diazepam for the measurement of diazepam and its major metabolite desmethyl diazepam. The mean clearance of diazepam was decreased by 27% and 38% and its half-life was increased by 36% and 39% after omeprazole and cimetidine, respectively. Neither drug had any apparent effect on the volume of distribution of diazepam. Desmethyldiazepam appeared more slowly after both omeprazole and cimetidine. It is concluded that the decrease in diazepam clearance was associated with inhibition of hepatic metabolism both by omeprazole and cimetidine. However, since diazepam has a wide therapeutic range, it is unlikely that concomitant treatment with therapeutically recommended doses of either omeprazole or cimetidine will result in a clinically significant interaction with diazepam.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Fellenius E, Berglindh T, Sachs G (1981) Substituted benzimida- zoles inhibit gastric acid secretion by blocking (H+K Nature 290:159–161
Wallmark B, Lorentzon P, Larsson H (1985) The mechanism of action of omeprazole — a survey of its inhibitory actions in vitro. Scand J Gastroentero1 20 [Suppl 108]:37–51
Dickins M, Bridges JW (1982) The relationship between the binding of 2-n-alkylbenzimidazoles to rat hepatic microsomal cytochrome P-450 and the inhibition of monooxygenation. Biochem Pharmaco1 31:1315–1320
Greene W (1984) Drug interactions involving cimetidine — mechanisms, documentation, implications. Drug Metab Drug Interact 5:25–51
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
SutfinT, 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
Gugler R, Jensen JC (1987) Drugs other than H2-receptor anta- gonists as clinically important inhibitors of drug metabolismin vivo. Pharmacol Ther 33:133–137
Henry D, Brent E Whyte I, Mihaly G, Devenish-Meares S (1987) Propranolol steady-state pharmacokinetics are unaltered by omeprazole. Eur J Clin Pharmaco1 33:369–373
Lagerström P-O, Persson B-A (1984) Determination of ome- prazole and metabolites in plasma and urine by liquid chroma- tography. J Chromatogr 309:347–356
Larsson R,Erlandsson P, Bodemar G, Norlander B, Fransson L, Strouth L (1982) Pharmacokinetics of cimetidine and its sul- phoxide metabolite during haemodialys. Eur J Clin Pharmacol 21:325–330
Yamaoka K, Nakagawa T, Uno T (1978) Statistical moments in pharmacokinetics. J Pharm Biopharm 6: 547–558
Fleiss J (1986) The design and analysis of clinical experiments. Wiley, New York 220–223
Klotz U, Reimann I (1980) Delayed clearance of diazepam due to cimetidine. N Engl J Med 302:1012–1014
Greenblatt D, AbernethyD, Morse D, HarmatzJ, Shader R (1984) Clinical importance of the interaction of diazepam and cimetidine. N Engl J Med 310:1639–1643
Henry DA, Somerville KW, Kitchingman GK, Langman MJS (1984) Omeprazole: effects on oxidative drug metabolism. Br J Clin Pharmacol 18:195–200
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Andersson, T., Andrén, K., Cederberg, C. et al. Effect of omeprazole and cimetidine on plasma diazepam levels . Eur J Clin Pharmacol 39, 51–54 (1990). https://doi.org/10.1007/BF02657057
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02657057