Sulfamethoxazole is metabolized to the hydroxylamine in humans
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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SMX is metabolized by cytochrome P450-mediated oxidation to form SMX-hydroxylamine (SMX-HA).
“SMX is metabolized by N-acetyltransferases (NAT1/NAT2) to form N4-acetyl sulfamethoxazole (NA-SMX), and by cytochrome P450-mediated oxidation to form SMX-hydroxylamine (SMX-HA).”
From N-Acetyltransferase (NAT) 1 and NAT2 Enzyme Activities Drive Interindividual Variability in Sulfamethoxazole N-Acetylation (2025) · cites this paper as [13]
SMX can produce chemically reactive metabolites, which may contribute to toxicity mechanisms.
“SMX can produce chemically reactive metabolites, which may contribute to toxicity mechanisms.”
From N-Acetyltransferase (NAT) 1 and NAT2 Enzyme Activities Drive Interindividual Variability in Sulfamethoxazole N-Acetylation (2025) · cites this paper as [13]
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- Authors
- Cribb, A. E., & Spielberg, S. P.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Spielberg, Stephen P
- ORCID
- Cribb, Alastair E
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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