Abstract
FUROSEMIDE (frusemide) is a diuretic drug frequently used in the treatment of many cardiovascular and renal diseases. Its use is contraindicated in pregnancy because of its recognised teratogenic potential1. The drug also has been reported to potentiate renal injury when used in combination with cephaloridine2,3. Here we report that this widely prescribed therapeutic agent is converted by microsomal enzymes in the liver of mice and humans to a reactive arylating metabolite that produces massive hepatic necrosis in mice.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Physicians Desk Reference 774 (Medical Economics Co., Oradell, New Jersey, 1973).
Dodds, M. G., and Foord, R. D., Br. J. Pharmac., 40, 227–236 (1970).
Foord, R. D., Proc. 6th Int. Cong. Chemother., Tokyo, 1, 597–604 (1969).
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Davis, D. C., Gillette, J. R., and Brodie, B. B., J. Pharmac. exp. Ther., 187, 185–194 (1973).
Potter, W. Z., Nelson, W. L., Thoreirsson, S. S., Sasame, H., Jollow, D. J., and Mitchell, J. R., Fedn Proc., 32, 305 (1973).
Weihe, M., Potter, W. Z., Nelson, W. L., Jollow, D. J., and Mitchell, J. R., Tox. appl. Pharmac. (in the press).
Jollow, D. J., Mitchell, J. R., Potter, W. Z., Davis, D. C., Gillette, J. R., and Brodie, B. B., J. Pharmac. exp. Ther., 187, 195–202 (1973).
Potter, W. Z., Davis, D. C., Mitchell, J. R., Jollow, D. J., Gillette, J. R., and Brodie, B. B., J. Pharmac. exp. Ther., 187, 203–210 (1973).
Thorgeirsson, S. S., Sasame, H., Potter, W. Z., Nelson, W. L., Jollow, D. J., and Mitchell, J. R., Fedn Proc., 32, 305 (1973).
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gillette, J. R., and Brodie, B. B., J. Pharmac. exp. Ther., 187, 211–217 (1973).
Swenson, D. H., Miller, J. A., and Miller, E. C., Biochem. biophys. Res., Commun., 53, 1260–1267 (1973).
Seawright, A. A., and Mattocks, A. R., Experientia, 29, 1197–1200 (1973).
Seawright, A. A., and Hrdlicka, J., Br. J. exp. Path., 53, 242–252 (1972).
Wilson, B. J., Yang, D. T. C., and Boyd, M. R., Nature, 227, 521–523 (1970).
Wilson, B. J., Boyd, M. R., Harris, T. M., and Yang, D. T. C., Nature, 231, 52–53 (1971).
Kindt, H., and Schmidt, E., Pharmacologia Clinica, 2, 221–226 (1970).
Frusemide in Renal Failure (edit. by Elliott, R. W., Kerrand, D. N. S., and Lewis, A. A. G.), Postgrad. med. J. Suppl., 47, 5–57 (1971).
Miller, J. A., Cancer Res., 30, 559–576 (1970).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
MITCHELL, J., POTTER, W., HINSON, J. et al. Hepatic necrosis caused by furosemide. Nature 251, 508–511 (1974). https://doi.org/10.1038/251508a0
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1038/251508a0
- Springer Nature Limited
This article is cited by
-
A history of the roles of cytochrome P450 enzymes in the toxicity of drugs
Toxicological Research (2021)
-
Metabolic activation of furan moiety makes Diosbulbin B hepatotoxic
Archives of Toxicology (2016)
-
An end to the search for new drugs?
Nature (1982)
-
Pulmonary bronchiolar alkylation and necrosis by 3-methylfuran, a naturally occurring potential atmospheric contaminant
Nature (1978)
-
Hepatic injury and drug metabolism in patients with alpha-methyldopa-induced liver damage
European Journal of Clinical Pharmacology (1977)