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. 1984 Dec;18(6):907–914. doi: 10.1111/j.1365-2125.1984.tb02563.x

Cimetidine alters pethidine disposition in man.

D R Guay, R C Meatherall, J L Chalmers, G R Grahame
PMCID: PMC1463672  PMID: 6529532

Abstract

The effect of concurrent cimetidine administration on the disposition of pethidine was investigated in eight healthy male volunteers (18-31 years). The subjects received 70 mg i.v. pethidine HCl doses before and during cimetidine treatment (1200 mg/day p.o.). During cimetidine treatment, pethidine total body clearance (CL) decreased by 22% (0.611 +/- 0.101 [mean +/- s.d.] to 0.474 +/- 0.098 1 kg-1 h, P less than 0.05) and pethidine volume of distribution at steady state (Vss) decreased by 13% (4.79 +/- 0.82 to 4.16 +/- 0.75 l/kg, P less than 0.05). A cimetidine-induced reduction in pethidine oxidation to norpethidine was suggested by a 23% reduction in norpethidine area under the curve from 0 to 24 h (472 +/- 93 to 362 +/- 38 ng ml-1 h, P less than 0.05) and a 29% reduction in peak norpethidine concentration (26.7 +/- 5.3 to 18.9 +/- 1.9 ng/ml, P less than 0.05). There were no significant linear correlations of serum trough cimetidine concentration with percentage reductions in pethidine CL, pethidine Vss, norpethidine AUC (24), or norpethidine peak concentrations. It would appear that the cimetidine-pethidine kinetic interaction may be of sufficient magnitude to be clinically significant. Caution is advised when patients are treated concurrently with these two agents.

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Selected References

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  1. Austin K. L., Stapleton J. V., Mather L. E. Rate of formation of norpethidine from pethidine. Br J Anaesth. 1981 Mar;53(3):255–258. doi: 10.1093/bja/53.3.255. [DOI] [PubMed] [Google Scholar]
  2. Benet L. Z., Galeazzi R. L. Noncompartmental determination of the steady-state volume of distribution. J Pharm Sci. 1979 Aug;68(8):1071–1074. doi: 10.1002/jps.2600680845. [DOI] [PubMed] [Google Scholar]
  3. Berkowitz B. A. The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin Pharmacokinet. 1976;1(3):219–230. doi: 10.2165/00003088-197601030-00004. [DOI] [PubMed] [Google Scholar]
  4. Davis T. G., Pickett D. L., Schlosser J. H. Evaluation of a worldwide spontaneous reporting system with cimetidine. JAMA. 1980 May 16;243(19):1912–1914. [PubMed] [Google Scholar]
  5. Edwards D. J., Svensson C. K., Visco J. P., Lalka D. Clinical pharmacokinetics of pethidine: 1982. Clin Pharmacokinet. 1982 Sep-Oct;7(5):421–433. doi: 10.2165/00003088-198207050-00003. [DOI] [PubMed] [Google Scholar]
  6. Feely J. Interaction of cimetidine with other drugs. South Med J. 1983 Jun;76(6):753–758. doi: 10.1097/00007611-198306000-00020. [DOI] [PubMed] [Google Scholar]
  7. Feely J., Wilkinson G. R., McAllister C. B., Wood A. J. Increased toxicity and reduced clearance of lidocaine by cimetidine. Ann Intern Med. 1982 May;96(5):592–594. doi: 10.7326/0003-4819-96-5-592. [DOI] [PubMed] [Google Scholar]
  8. Feely J., Wilkinson G. R., Wood A. J. Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med. 1981 Mar 19;304(12):692–695. doi: 10.1056/NEJM198103193041202. [DOI] [PubMed] [Google Scholar]
  9. Fine A., Churchill D. N. Potentially lethal interaction of cimetidine and morphine. Can Med Assoc J. 1981 Jun 1;124(11):1434–1436. [PMC free article] [PubMed] [Google Scholar]
  10. Freston J. W. Cimetidine. I. Developments, pharmacology, and efficacy. Ann Intern Med. 1982 Oct;97(4):573–580. doi: 10.7326/0003-4819-97-4-573. [DOI] [PubMed] [Google Scholar]
  11. Gilbert P. E., Martin W. R. Antagonism of the convulsant effects of heroin, d-propoxyphene, meperidine, normeperidine and thebaine by naloxone in mice. J Pharmacol Exp Ther. 1975 Mar;192(3):538–541. [PubMed] [Google Scholar]
  12. Guay D. R., Bockbrader H. N., Matzke G. R. High-performance liquid chromatographic analysis of cimetidine in serum and urine. J Chromatogr. 1982 Mar 12;228:398–403. doi: 10.1016/s0378-4347(00)80462-4. [DOI] [PubMed] [Google Scholar]
  13. Henderson J. M., Ibrahim S. Z., Millikan W. J., Jr, Santi M., Warren W. D. Cimetidine does not reduce liver blood flow in cirrhosis. Hepatology. 1983 Nov-Dec;3(6):919–922. doi: 10.1002/hep.1840030605. [DOI] [PubMed] [Google Scholar]
  14. Kaiko R. F., Foley K. M., Grabinski P. Y., Heidrich G., Rogers A. G., Inturrisi C. E., Reidenberg M. M. Central nervous system excitatory effects of meperidine in cancer patients. Ann Neurol. 1983 Feb;13(2):180–185. doi: 10.1002/ana.410130213. [DOI] [PubMed] [Google Scholar]
  15. Knodell R. G., Holtzman J. L., Crankshaw D. L., Steele N. M., Stanley L. N. Drug metabolism by rat and human hepatic microsomes in response to interaction with H2-receptor antagonists. Gastroenterology. 1982 Jan;82(1):84–88. [PubMed] [Google Scholar]
  16. MILLER J. W., ANDERSON H. H. The effect of N-demethylation on certain pharmacologic actions of morphine, codeine, and meperidine in the mouse. J Pharmacol Exp Ther. 1954 Oct;112(2):191–196. [PubMed] [Google Scholar]
  17. Mojaverian P., Fedder I. L., Vlasses P. H., Rotmensch H. H., Rocci M. L., Jr, Swanson B. N., Ferguson R. K. Cimetidine does not alter morphine disposition in man. Br J Clin Pharmacol. 1982 Dec;14(6):809–813. doi: 10.1111/j.1365-2125.1982.tb02041.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moore A., Sear J., Baldwin D., Allen M., Hunniset A., Bullingham R., McQuay H. Morphine kinetics during and after renal transplantation. Clin Pharmacol Ther. 1984 May;35(5):641–645. doi: 10.1038/clpt.1984.88. [DOI] [PubMed] [Google Scholar]
  19. Somogyi A., Gugler R. Clinical pharmacokinetics of cimetidine. Clin Pharmacokinet. 1983 Nov-Dec;8(6):463–495. doi: 10.2165/00003088-198308060-00001. [DOI] [PubMed] [Google Scholar]
  20. Somogyi A., Gugler R. Drug interactions with cimetidine. Clin Pharmacokinet. 1982 Jan-Feb;7(1):23–41. doi: 10.2165/00003088-198207010-00002. [DOI] [PubMed] [Google Scholar]
  21. Sorkin E. M., Darvey D. L. Review of cimetidine drug interactions. Drug Intell Clin Pharm. 1983 Feb;17(2):110–120. doi: 10.1177/106002808301700205. [DOI] [PubMed] [Google Scholar]
  22. Sorkin E. M., Ogawa G. S. Cimetidine potentiation of narcotic action. Drug Intell Clin Pharm. 1983 Jan;17(1):60–61. doi: 10.1177/106002808301700120. [DOI] [PubMed] [Google Scholar]
  23. Szeto H. H., Inturrisi C. E., Houde R., Saal S., Cheigh J., Reidenberg M. M. Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure of cancer. Ann Intern Med. 1977 Jun;86(6):738–741. doi: 10.7326/0003-4819-86-6-738. [DOI] [PubMed] [Google Scholar]
  24. Verbeeck R. K., Branch R. A., Wilkinson G. R. Meperidine disposition in man: influence of urinary pH and route of administration. Clin Pharmacol Ther. 1981 Nov;30(5):619–628. doi: 10.1038/clpt.1981.213. [DOI] [PubMed] [Google Scholar]
  25. Wilkinson G. R. Pharmacokinetics of drug disposition: hemodynamic considerations. Annu Rev Pharmacol. 1975;15:11–27. doi: 10.1146/annurev.pa.15.040175.000303. [DOI] [PubMed] [Google Scholar]
  26. Wilkinson G. R., Shand D. G. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther. 1975 Oct;18(4):377–390. doi: 10.1002/cpt1975184377. [DOI] [PubMed] [Google Scholar]
  27. Wing L. M., Miners J. O., Birkett D. J., Foenander T., Lillywhite K., Wanwimolruk S. Lidocaine disposition--sex differences and effects of cimetidine. Clin Pharmacol Ther. 1984 May;35(5):695–701. doi: 10.1038/clpt.1984.97. [DOI] [PubMed] [Google Scholar]

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