Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1991 Mar;31(3):251–255. doi: 10.1111/j.1365-2125.1991.tb05525.x

Iron supplements: a common cause of drug interactions.

N R Campbell 1, B B Hasinoff 1
PMCID: PMC1368348  PMID: 2054263

Abstract

Iron-drug interactions of clinical significance may occur in many patients and involve a large number of therapies. Concurrent ingestion of iron causes marked decreases in the bioavailability of a number of drugs. The affected drugs, tetracycline, tetracycline derivatives (doxycycline, methacycline and oxytetracycline), penicillamine, methyldopa, levodopa, carbidopa and ciprofloxacin have diverse chemical structures and clinical effects. The major mechanism of these drug interactions is the formation of iron-drug complexes (chelation or binding of iron by the involved drug). A large number of other important and commonly used drugs such as thyroxine, captopril and folic acid have been demonstrated to form stable complexes with iron. There is little known about the effects of concurrent therapy with iron supplements for most of the drugs.

Full text

PDF
251

Selected References

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

  1. ALBERT A., REES C. W. Avidity of the tetracyclines for the cations of metals. Nature. 1956 Mar 3;177(4505):433–434. doi: 10.1038/177433a0. [DOI] [PubMed] [Google Scholar]
  2. Campbell N. R., Dunnette J. H., Mwaluko G., Van Loon J., Weinshilboum R. M. Platelet phenol sulfotransferase and erythrocyte catechol-O-methyltransferase activities: correlation with methyldopa metabolism. Clin Pharmacol Ther. 1984 Jan;35(1):55–63. doi: 10.1038/clpt.1984.9. [DOI] [PubMed] [Google Scholar]
  3. Campbell N. R., Hasinoff B. Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism. Clin Pharmacol Ther. 1989 Mar;45(3):220–225. doi: 10.1038/clpt.1989.21. [DOI] [PubMed] [Google Scholar]
  4. Campbell N. R., Rankine D., Goodridge A. E., Hasinoff B. B., Kara M. Sinemet-ferrous sulphate interaction in patients with Parkinson's disease. Br J Clin Pharmacol. 1990 Oct;30(4):599–605. doi: 10.1111/j.1365-2125.1990.tb03819.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Campbell N., Paddock V., Sundaram R. Alteration of methyldopa absorption, metabolism, and blood pressure control caused by ferrous sulfate and ferrous gluconate. Clin Pharmacol Ther. 1988 Apr;43(4):381–386. doi: 10.1038/clpt.1988.47. [DOI] [PubMed] [Google Scholar]
  6. Campbell R. R., Hasinoff B., Chernenko G., Barrowman J., Campbell N. R. The effect of ferrous sulfate and pH on L-dopa absorption. Can J Physiol Pharmacol. 1990 May;68(5):603–607. doi: 10.1139/y90-087. [DOI] [PubMed] [Google Scholar]
  7. Cole A., May P. M., Williams D. R. Metal binding by pharmaceuticals. Part 1. Copper(II) and zinc(II) interactions following ethambutol administration. Agents Actions. 1981 May;11(3):296–305. doi: 10.1007/BF01967631. [DOI] [PubMed] [Google Scholar]
  8. Conrad M. E., Schade S. G. Ascorbic acid chelates in iron absorption: a role for hydrochloric acid and bile. Gastroenterology. 1968 Jul;55(1):35–45. [PubMed] [Google Scholar]
  9. Fujita Y., Mori I., Fujita K., Kitano S., Tanaka T. A color reaction of 1,2-diphenols based on colored complex formation with phenylfluorone and iron(III) and its application to the assay of catecholamines in pharmaceutical preparations. Chem Pharm Bull (Tokyo) 1985 Dec;33(12):5385–5392. doi: 10.1248/cpb.33.5385. [DOI] [PubMed] [Google Scholar]
  10. Gothoni G., Neuvonen P. J., Mattila M., Hackman R. Iron-tetracycline interaction: effect of time interval between the drugs. Acta Med Scand. 1972 May;191(5):409–411. [PubMed] [Google Scholar]
  11. Greenberger N. J., Ruppert R. D., Cuppage F. E. Inhibition of intestinal iron transport induced by tetracycline. Gastroenterology. 1967 Oct;53(4):590–599. [PubMed] [Google Scholar]
  12. Issopoulos P. B. Spectrophotometric determination of trace amounts of iron(III) with norfloxacin as complexing reagent. Analyst. 1989 May;114(5):627–630. doi: 10.1039/an9891400627. [DOI] [PubMed] [Google Scholar]
  13. Lacroix C., Cerutti F., Nouveau J., Menager S., Lafont O. Détermination de l'éthambutol plasmatique par chromatographie liquide et détection spectrophotométrique ultraviolette. J Chromatogr. 1987 Mar 20;415(1):85–94. [PubMed] [Google Scholar]
  14. Lyle W. H. Penicillamine and iron. Lancet. 1976 Aug 21;2(7982):420–420. doi: 10.1016/s0140-6736(76)92438-7. [DOI] [PubMed] [Google Scholar]
  15. McCallister J. D., Chin T. F., Lach J. L. Diffuse reflectance studies of solid-solid interactions. IV. Interaction of bishydroxycoumarin, furosemide, and other medicinal agents with various adjuvants. J Pharm Sci. 1970 Sep;59(9):1286–1289. doi: 10.1002/jps.2600590916. [DOI] [PubMed] [Google Scholar]
  16. McElnay J. C., Harron D. W., D'Arcy P. F., Collier P. S. The interaction of warfarin with antacid constituents in the gut. Experientia. 1979 Oct 15;35(10):1359–1360. doi: 10.1007/BF01964007. [DOI] [PubMed] [Google Scholar]
  17. Neuvonen P. J., Gothoni G., Hackman R., Björksten K. Interference of iron with the absorption of tetracyclines in man. Br Med J. 1970 Nov 28;4(5734):532–534. doi: 10.1136/bmj.4.5734.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nutt J. G., Fellman J. H. Pharmacokinetics of levodopa. Clin Neuropharmacol. 1984;7(1):35–49. doi: 10.1097/00002826-198403000-00002. [DOI] [PubMed] [Google Scholar]
  19. Osman M. A., Patel R. B., Schuna A., Sundstrom W. R., Welling P. G. Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate. Clin Pharmacol Ther. 1983 Apr;33(4):465–470. doi: 10.1038/clpt.1983.63. [DOI] [PubMed] [Google Scholar]
  20. Polk R. E., Healy D. P., Sahai J., Drwal L., Racht E. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother. 1989 Nov;33(11):1841–1844. doi: 10.1128/aac.33.11.1841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rajan K. S., Manian A. A., Davis J. M., Dekirmenjian H. Metal chelates of L-DOPA for improved replenishment of dopaminergic pools. Brain Res. 1976 May 7;107(2):317–331. doi: 10.1016/0006-8993(76)90229-8. [DOI] [PubMed] [Google Scholar]
  22. Rosowsky A., Freisheim J. H., Moran R. G., Solan V. C., Bader H., Wright J. E., Radike-Smith M. Methotrexate analogues. 26. Inhibition of dihydrofolate reductase and folylpolyglutamate synthetase activity and in vitro tumor cell growth by methotrexate and aminopterin analogues containing a basic amino acid side chain. J Med Chem. 1986 May;29(5):655–660. doi: 10.1021/jm00155a012. [DOI] [PubMed] [Google Scholar]
  23. Southorn P. A., Powis G. Free radicals in medicine. I. Chemical nature and biologic reactions. Mayo Clin Proc. 1988 Apr;63(4):381–389. doi: 10.1016/s0025-6196(12)64861-7. [DOI] [PubMed] [Google Scholar]
  24. Timmers K., Sternglanz R. Ionization and divalent cation dissociation constants of nalidixic and oxolinic acids. Bioinorg Chem. 1978 Aug;9(2):145–155. doi: 10.1016/s0006-3061(00)80286-0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES