NEIL H. SHEAR, M.D.; STEPHEN P. SPIELBERG, M.D., Ph.D.; DENIS M. GRANT, Ph.D.; BING K. TANG, Ph.D.; WERNER KALOW, M.D.
Individual differences in metabolism of the sulfonamides may predispose patients to idiosyncratic reactions. Sulfonamides are metabolized by N-acetylation (mediated by a genetically polymorphic enzyme) and oxidation to potentially toxic metabolites. We examined 6 patients who had severe reactions to sulfonamides and compared them with 20 controls. Acetylator phenotype was determined with caffeine, a safe in-vivo probe of enzyme activity. All 6 patients were slow acetylators (expected, 55%; p < 0.05). Detoxification of oxidative metabolites was studied in vitro with a lymphocyte assay evaluating cell death from metabolites generated by a murine hepatic microsomal system. Cells from each patient showed increased toxicity from sulfonamide metabolites but not from the drugs themselves. Cells from parents of 3 patients had intermediate toxicity from sulfonamide metabolites, whereas cells from a sibling of 1 patient had a normal response. Susceptibility to sulfonamide reactions may be due to interaction of metabolic pathways, possibly under genetic control, regulating N-acetylation and specific detoxification of toxic metabolites of the drugs.
Learn more about subscription options.
Register Now for a free account.
SHEAR NH, SPIELBERG SP, GRANT DM, TANG BK, KALOW W. Differences in Metabolism of Sulfonamides Predisposing to Idiosyncratic Toxicity. Ann Intern Med. 1986;105:179–184. doi: 10.7326/0003-4819-105-2-179
Download citation file:
Published: Ann Intern Med. 1986;105(2):179-184.
Emergency Medicine, Hospital Medicine.
Results provided by:
Copyright © 2017 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use
This PDF is available to Subscribers Only