Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1983 Mar;23(3):458–464. doi: 10.1128/aac.23.3.458

Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics.

F G Hayden, H E Hoffman, D A Spyker
PMCID: PMC184669  PMID: 6847173

Abstract

In a double-blind, placebo-controlled study, the comparative toxicities and blood concentrations of amantadine hydrochloride and rimantadine hydrochloride were determined. Healthy, working adults ingested either 200 (n = 52) or 300 mg (n = 196) per day in divided doses for 4.5 days. Mean plasma drug concentrations at 4 h after the first dose were lower in rimantadine recipients given 100- (140 versus 300 ng/ml for rimantadine and amantadine, respectively; P less than 10(-5)) or 200-mg doses (310 versus 633 ng/ml; P less than 10(-5)). The plasma drug concentrations after the first dose correlated significantly with total symptom sources for both amantadine and rimantadine, but the plasma levels of toxic and nontoxic subjects overlapped extensively. At 300-mg/day dosage amantadine was associated more often with adverse central nervous system symptoms (33% of amantadine versus 9% of rimantadine recipients; P less than 0.001) and sleep disturbance (39 versus 13%; P less than 0.001), but not gastrointestinal symptoms (19.5 versus 16.0%). However, no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations. Amantadine and rimantadine differ in their pharmacokinetics but not in their potential for side effects at comparable plasma concentrations.

Full text

PDF
458

Selected References

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

  1. Aldrich P. E., Hermann E. C., Meier W. E., Paulshock M., Prichard W. W., Snyder J. A., Watts J. C. Antiviral agents. 2. Structure-activity relationships of compounds related to 1-adamantanamine. J Med Chem. 1971 Jun;14(6):535–543. doi: 10.1021/jm00288a019. [DOI] [PubMed] [Google Scholar]
  2. Armbruster K. F., Rahn A. C., Ing T. S., Halper I. S., Oyama J. H., Klawans H. L. Amantadine toxicity in a patient with renal insufficiency. Nephron. 1974;13(2):183–186. doi: 10.1159/000180391. [DOI] [PubMed] [Google Scholar]
  3. Bleidner W. E., Harmon J. B., Hewes W. E., Lynes T. E., Hermann E. C. Absorption, distribution and excretion of amantadine hydrochloride. J Pharmacol Exp Ther. 1965 Dec;150(3):484–490. [PubMed] [Google Scholar]
  4. 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]
  5. Fahn S., Craddock G., Kumin G. Acute toxic psychosis from suicidal overdosage of amantadine. Arch Neurol. 1971 Jul;25(1):45–48. doi: 10.1001/archneur.1971.00490010055008. [DOI] [PubMed] [Google Scholar]
  6. Greenblatt D. J., DiMascio A., Harmatz J. S., Bernardo D. L., Marder J. E. Pharmacokinetics and clinical effects of amantadine in drug-induced extrapyramidal symptoms. J Clin Pharmacol. 1977 Nov-Dec;17(11-12):704–708. doi: 10.1002/j.1552-4604.1977.tb01545.x. [DOI] [PubMed] [Google Scholar]
  7. Grelak R. P., Clark R., Stump J. M., Vernier V. G. Amantadine-dopamine interaction: possible mode of action in Parkinsonism. Science. 1970 Jul 10;169(3941):203–204. doi: 10.1126/science.169.3941.203. [DOI] [PubMed] [Google Scholar]
  8. Hayden F. G., Gwaltney J. M., Jr, Van de Castle R. L., Adams K. F., Giordani B. Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults. Antimicrob Agents Chemother. 1981 Feb;19(2):226–233. doi: 10.1128/aac.19.2.226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Horadam V. W., Sharp J. G., Smilack J. D., McAnalley B. H., Garriott J. C., Stephens M. K., Prati R. C., Brater D. C. Pharmacokinetics of amantadine hydrochloride in subjects with normal and impaired renal function. Ann Intern Med. 1981 Apr;94(4 Pt 1):454–458. doi: 10.7326/0003-4819-94-4-454. [DOI] [PubMed] [Google Scholar]
  10. Ing T. S., Daugirdas J. T., Soung L. S., Klawans H. L., Mahurkar S. D., Hayashi J. A., Geis W. P., Hano J. E. Toxic effects of amantadine in patients with renal failure. Can Med Assoc J. 1979 Mar 17;120(6):695–698. [PMC free article] [PubMed] [Google Scholar]
  11. Jackson G. G., Stanley E. D. Prevention and control of influenza by chemoprophylaxis and chemotherapy. Prospects from examination of recent experience. JAMA. 1976 Jun 21;235(25):2739–2742. [PubMed] [Google Scholar]
  12. Matarazzo J. D., Wiens A. N., Matarazzo R. G., Goldstein S. G. Psychometric and clinical test-retest reliability of the Halstead impairment index in a sample of healthy, young, normal men. J Nerv Ment Dis. 1974 Jan;158(1):37–49. doi: 10.1097/00005053-197401000-00006. [DOI] [PubMed] [Google Scholar]
  13. Matin S. B., Rowland M. Electron-capture sensitivity comparison of various derivatives of primary and secondary amines. J Pharm Sci. 1972 Aug;61(8):1235–1240. doi: 10.1002/jps.2600610814. [DOI] [PubMed] [Google Scholar]
  14. Montanari C., Ferrari P., Bavazzano A. Urinary excretion of amantadine by the elderly. Eur J Clin Pharmacol. 1975 Jun 13;8(5):349–351. doi: 10.1007/BF00562661. [DOI] [PubMed] [Google Scholar]
  15. Monto A. S., Gunn R. A., Bandyk M. G., King C. L. Prevention of Russian influenza by amantadine. JAMA. 1979 Mar 9;241(10):1003–1007. [PubMed] [Google Scholar]
  16. Pacifici G. M., Nardini M., Ferrari P., Latini R., Fieschi C., Morselli P. L. Effect of amantadine on drug-induced parkisonism: relationship between plasma levels and effect. Br J Clin Pharmacol. 1976 Oct;3(5):883–889. doi: 10.1111/j.1365-2125.1976.tb00642.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Schwab R. S., Poskanzer D. C., England A. C., Jr, Young R. R. Amantadine in Parkinson's disease. Review of more than two years' experience. JAMA. 1972 Nov 13;222(7):792–795. doi: 10.1001/jama.222.7.792. [DOI] [PubMed] [Google Scholar]
  19. Sioufi A., Pommier F. Gas chromatographic determination of amantadine hydrochloride (Symmetrel) in human plasma and urine. J Chromatogr. 1980 Jul 11;183(1):33–39. doi: 10.1016/s0378-4347(00)81395-x. [DOI] [PubMed] [Google Scholar]
  20. Soung L. S., Ing T. S., Daugirdas J. T., Wu M. J., Gandhi V. C., Ivanovich P. T., Hano J. E., Viol G. W. Amantadine hydrochloride pharmacokinetics in hemodialysis patients. Ann Intern Med. 1980 Jul;93(1):46–49. doi: 10.7326/0003-4819-93-1-46. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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