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.
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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
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Published: Ann Intern Med. 1986;105(2):179-184.
Emergency Medicine, Hospital Medicine.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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