Cited by 175Pharmacogenetics and Drug MetabolismDrug-Induced Adverse ReactionsDrug-Induced Hepatotoxicity and Protection

Sulfamethoxazole is metabolized to the hydroxylamine in humans

Cribb, Alastair E, Spielberg, Stephen P·1992·Clinical Pharmacology and Therapeutics

Abstract

The oxidation of sulfamethoxazole to its hydroxylamine metabolite was investigated in vitro with human liver microsomes and in vivo by detection in the urine. Sulfamethoxazole was oxidized to the hydroxylamine in an NADPH-dependent process by liver microsomes prepared from two human livers. Three healthy volunteers ingested 1000 mg sulfamethoxazole, and urine was collected for 24 hours. Sulfamethoxazole hydroxylamine constituted 3.1% +/- 0.7% of the drug excreted in the urine in 24 hours. Fifty-four percent of the ingested dose was excreted during this same time period. We conclude that sulfamethoxazole hydroxylamine is an authentic in vivo metabolite in humans, probably formed predominantly by cytochrome P450 in the liver. It could be responsible for mediation of sulfonamide adverse reactions, particularly hypersensitivity reactions.

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Crossref · 10.1038/clpt.1992.57

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Authors
Cribb, A. E., & Spielberg, S. P.
Affiliations
University of Toronto (CA)
Corresponding author
Spielberg, Stephen P
Venue
Clinical Pharmacology and Therapeutics
Publisher
Wiley
Published
1992-05
Volume
51
Issue
5
Pages
522-526
ISSN
  • 0009-9236 (ISSN-L)
  • 1532-6535
OpenAlex
W2032455764
Cited by
175
References
0
Citations by year
2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 2 · 2019: 5 · 2018: 6 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 8 · 2013: 7 · 2012: 1
FWCI
6.91
Type
journal article
Language
en
Open access
closed
Locations
  • Clinical Pharmacology & Therapeutics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
Keywords
sulfamethoxazole, hydroxylamine metabolites, sulfonamide metabolism, human liver microsomes, NADPH-dependent oxidation, cytochrome P450, urinary excretion, hypersensitivity
MeSH terms
Adult, Biotransformation, Cytochrome P-450 Enzyme System, Humans, Male, Microsomes, Liver, NADP, Oxidation-Reduction, Sulfamethoxazole

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