Skip to main content
Log in

Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam

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

Summary

The pharmacokinetics of single oral doses of desmethyldiazepam 20 mg or oxazepam 50 mg were studied in 5 healthy volunteers under controlled conditions, before and following a 24 h pretreatment with cimetidine 200 mg×5. Cimetidine significantly impaired (p=0.03) the elimination of desmethyldiazepam, as shown prolongation of its elimination half-life from 51.7±21.9 h to 72.6±39.4 h (mean ± SD), and a decrease in total plasma clearance from 12.0±2.7 ml/min to 8.6±3.3 ml/min. The disposition of oxazepam was not affected. From these results, and recently published data on diazepam and chlordiazepoxide, it is concluded that cimetidine impairs the hepatic elimination of those benzodiazepines which are metabolized by phase I reactions.

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.

References

  1. Puurunen J, Pelkonen O (1979) Cimetidine inhibits microsomal drug metabolism in the rat. Eur J Pharmacol 55: 335–336

    PubMed  Google Scholar 

  2. Serlin MJ, Sibeon RB, Mossman S, Breckenridge AM, Williams JRB, Atwood JL, Willoughby JMT (1979) Cimetidine: Interaction with oral anticoagulants in man. Lancet 2: 317–319

    PubMed  Google Scholar 

  3. Puurunen I, Sotaniemi E, Pelkonen O (1979) Cimetidine inhibits microsomal metabolism in man. Naunyn-Schmiedeberg's Arch Pharmacol 308: R 24

  4. Klotz U, Reimann I (1980) Delayed clearance of diazepam due to cimetidine. N Engl J Med 302: 1012–1014

    PubMed  Google Scholar 

  5. Klotz U, Antilla VJ, Reimann I (1979) Cimetidine/diazepam interaction. Lancet 2: 699

    Google Scholar 

  6. Klotz U, Avant GR, Hoyumpa A, Schenker S, Wilkinson GR (1975) Effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55: 347–359

    PubMed  Google Scholar 

  7. Shull HJ, Wilkinson GR, Johnson RF, Schenker S (1976) Normal elimination of oxazepam in acute viral hepatitis and cirrhosis. Ann Intern Med 84: 420–425

    PubMed  Google Scholar 

  8. Westlake WJ (1970) Time integral of drug concentration in the central (plasma) compartment. J Pharm Sci 59: 722–723

    PubMed  Google Scholar 

  9. Gibaldi M, Nagashima R, Levy G (1969) Relationship between drug concentration in plasma or serum and amount of drug in the body. J Pharm Sci 58: 193–197

    Google Scholar 

  10. Desmond PV, Patwardhan RV, Schenker S, Speeg KV (1980) Cimetidine impairs the elimination of chlordiazepoxide in man. Ann Intern Med (in press)

  11. Kraus JW, Desmond PV, Marshall JP, Johnson RF, Schenker S, Wilkinson GR (1978) The effects of aging and liver disease on the disposition of lorazepam in man. Clin Pharmacol Ther 24: 411–419

    PubMed  Google Scholar 

  12. Klotz U, Müller-Seydlitz P (1979) Altered elimination of desmethyldiazepam in the elderly. Br J Clin Pharmacol 7: 119–120

    PubMed  Google Scholar 

  13. Roberts RK, Wilkinson GR, Branch RA, Schenker S (1978) The effect of age and parenchymal liver disease on the disposition and elimination of chlordiazepoxide. Gastroenterology 75: 479–485

    PubMed  Google Scholar 

  14. Klotz U, Antonin KH, Brügel H, Bieck PR (1977) Disposition of diazepam and its major metabolite desmethyldiazepam in patients with liver disease. Clin Pharmacol Ther 21: 430–436

    PubMed  Google Scholar 

  15. Rendić S, Šunjić V, Toso R, Kajfež Ruf HH (1979) Interaction of cimetidine with liver microsomes. Xenobiotica 9: 555–564

    PubMed  Google Scholar 

  16. Burland WL, Duncan WAM, Hesselbo T, Mills JG, Sharpe PC, Haggie SJ, Wyllie JH (1975) Pharmacological evaluation of cimetidine, a new histamine H2-receptor antagonist, in healthy man. Br J Clin Pharmacol 2: 481–486

    PubMed  Google Scholar 

  17. Spence RW, Celestin LR, de la Guardia R, MacMullen CA, McCormick DA (1977) Biliary secretion of cimetidine in man. In: Burland WL, Simkins MA (eds) Cimetidine. Proceedings of the Second International Symposium on Histamine H2-receptor Antagonists. Excerpta Medica, Amsterdam, pp 81–84

    Google Scholar 

  18. Patwardhan RV, Yarborough GW, Desmond PV, Johnson RF, Schenker S, Speeg Jr KV (1980) Cimetidine spares in the glucuronidation of lorazepam and oxazepam in man. Gastroenterology (in press)

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klotz, U., Reimann, I. Influence of cimetidine on the pharmacokinetics of desmethyldiazepam and oxazepam. Eur J Clin Pharmacol 18, 517–520 (1980). https://doi.org/10.1007/BF00874666

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00874666

Key words

Navigation