Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1989 Jun;33(6):820–823. doi: 10.1128/aac.33.6.820

Effect of cimetidine on the disposition of rimantadine in healthy subjects.

A A Holazo 1, N Choma 1, S Y Brown 1, L F Lee 1, R J Wills 1
PMCID: PMC284238  PMID: 2764530

Abstract

Twenty-three healthy male and female subjects received single 100-mg oral doses of rimantadine hydrochloride on two occasions in an open-label, sequential design with a 6-day washout between doses. The first dose of rimantadine was administered alone, and the second dose was administered concomitantly with cimetidine (300 mg four times a day for 6 days). Blood and urine samples were collected, and rimantadine concentrations were determined by a gas-chromatographic--mass-spectrometric method. There were no changes in the rate of absorption and the renal clearance of rimantadine when it was administered with cimetidine. Both parametric and nonparametric tests showed significant differences in the area under the concentration-time curve, apparent total clearance, and elimination rate constant between the treatments (P less than 0.01). The apparent total clearance was reduced by 18%, resulting in higher values for the area under the concentration-time curve in the presence of cimetidine. However, the wide therapeutic index of rimantadine renders these changes of little, if any, clinical consequence.

Full text

PDF
820

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Dawkins A. T., Jr, Gallager L. R., Togo Y., Hornick R. B., Harris B. A. Studies on induced influenza in man. II. Double-blind study designed to assess the prophylactic efficacy of an analogue of amantadine hydrochloride. JAMA. 1968 Mar 25;203(13):1095–1099. doi: 10.1001/jama.203.13.1095. [DOI] [PubMed] [Google Scholar]
  2. Dolin R., Reichman R. C., Madore H. P., Maynard R., Linton P. N., Webber-Jones J. A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. N Engl J Med. 1982 Sep 2;307(10):580–584. doi: 10.1056/NEJM198209023071002. [DOI] [PubMed] [Google Scholar]
  3. Feely J., Pereira L., Guy E., Hockings N. Factors affecting the response to inhibition of drug metabolism by cimetidine--dose response and sensitivity of elderly and induced subjects. Br J Clin Pharmacol. 1984 Jan;17(1):77–81. doi: 10.1111/j.1365-2125.1984.tb05002.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Fukuda E. K., Rodriguez L. C., Choma N., Keigher N., De Grazia F., Garland W. A. Quantitative determination of rimantadine in human plasma and urine by GC-MS. Biomed Environ Mass Spectrom. 1987 Oct;14(10):549–553. doi: 10.1002/bms.1200141004. [DOI] [PubMed] [Google Scholar]
  5. Hayden F. G., Cote K. M., Douglas R. G., Jr Plaque inhibition assay for drug susceptibility testing of influenza viruses. Antimicrob Agents Chemother. 1980 May;17(5):865–870. doi: 10.1128/aac.17.5.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Patriarca P. A., Kater N. A., Kendal A. P., Bregman D. J., Smith J. D., Sikes R. K. Safety of prolonged administration of rimantadine hydrochloride in the prophylaxis of influenza A virus infections in nursing homes. Antimicrob Agents Chemother. 1984 Jul;26(1):101–103. doi: 10.1128/aac.26.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Quarles J. M., Couch R. B., Cate T. R., Goswick C. B. Comparison of amantadine and rimantadine for prevention of type A (Russian) influenza. Antiviral Res. 1981 Sep;1(3):149–155. doi: 10.1016/0166-3542(81)90003-6. [DOI] [PubMed] [Google Scholar]
  9. Rabinovich S., Baldini J. T., Bannister R. Treatment of influenza. The therapeutic efficacy of rimantadine HC1 in a naturally occurring influenza A2 outbreak. Am J Med Sci. 1969 May;257(5):328–335. doi: 10.1097/00000441-196905000-00005. [DOI] [PubMed] [Google Scholar]
  10. Röllinghoff W., Paumgartner G. Inhibition of drug metabolism by cimetidine in man: dependence on pretreatment microsomal liver function. Eur J Clin Invest. 1982 Oct;12(5):429–432. doi: 10.1111/j.1365-2362.1982.tb00691.x. [DOI] [PubMed] [Google Scholar]
  11. Somogyi A., Muirhead M. Pharmacokinetic interactions of cimetidine 1987. Clin Pharmacokinet. 1987 May;12(5):321–366. doi: 10.2165/00003088-198712050-00002. [DOI] [PubMed] [Google Scholar]
  12. Van Voris L. P., Betts R. F., Hayden F. G., Christmas W. A., Douglas R. G., Jr Successful treatment of naturally occurring influenza A/USSR/77 H1N1. JAMA. 1981 Mar 20;245(11):1128–1131. doi: 10.1001/jama.245.11.1128. [DOI] [PubMed] [Google Scholar]
  13. Wills R. J., Belshe R., Tomlinsin D., De Grazia F., Lin A., Wells S., Milazzo J., Berry C. Pharmacokinetics of rimantadine hydrochloride in patients with chronic liver disease. Clin Pharmacol Ther. 1987 Oct;42(4):449–454. doi: 10.1038/clpt.1987.176. [DOI] [PubMed] [Google Scholar]
  14. Wills R. J., Choma N., Buonpane G., Lin A., Keigher N. Relative bioavailability of rimantadine HCl tablet and syrup formulations in healthy subjects. J Pharm Sci. 1987 Dec;76(12):886–888. doi: 10.1002/jps.2600761208. [DOI] [PubMed] [Google Scholar]
  15. Wills R. J., Farolino D. A., Choma N., Keigher N. Rimantadine pharmacokinetics after single and multiple doses. Antimicrob Agents Chemother. 1987 May;31(5):826–828. doi: 10.1128/aac.31.5.826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wingfield W. L., Pollack D., Grunert R. R. Therapeutic efficacy of amantadine HCl and rimantadine HCl in naturally occurring influenza A2 respiratory illness in man. N Engl J Med. 1969 Sep 11;281(11):579–584. doi: 10.1056/NEJM196909112811102. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES