Urinary recovery and kinetics of sulphamethoxazole and its metabolites in HIV-seropositive patients and healthy volunteers after a single oral dose of sulphamethoxazole
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1. The urinary excretion of sulphamethoxazole and its metabolites was compared between healthy volunteers and HIV-seropositive patients in order to get a better understanding of why HIV seropositives are more predisposed to idiosyncratic toxicity of sulphonamides. 2. A single 800 mg oral dose of sulphamethoxazole was administered to seven healthy volunteers and seven asymptomatic HIV seropositives without previous use of sulphonamides. 3. Urine was collected for 4 days and drug analysis was by h.p.l.c. 4. No difference was observed between seropositive and seronegative individuals in the urinary recovery of sulphamethoxazole, N4-acetyl-, 5-hydroxy-, N4-acetyl-5-hydroxy-sulphamethoxazole and the N1-glucuronide conjugate. However the recovery of the hydroxylamine metabolite of sulphamethoxazole was significantly lower in the HIV seropositives (0.50 +/- 0.51 vs 2.23 +/- 0.85%; 95% CI on the difference, -0.90 to -2.55; P = 0.0006). 5. Sulphamethoxazole hydroxylamine may be a factor in the susceptibility of HIV infected individuals to sulphonamides.
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NA-SMX accounts for approximately 44% of renally excreted metabolites, while parent SMX constitutes about 14% of drug-related material, and SMX-HA accounts for roughly 2% of urinary metabolites.
“NA-SMX accounts for approximately 44% of renally excreted metabolites, while the parent SMX constitutes about 14% of drug-related material, and SMX-HA accounts for roughly 2% of urinary metabolites.21,22”
From N-Acetyltransferase (NAT) 1 and NAT2 Enzyme Activities Drive Interindividual Variability in Sulfamethoxazole N-Acetylation (2025) · cites this paper as [21]
The Results and Discussion report urinary recovery of parent SMX, N4-SMX, and the hydroxylamine metabolite, but the available passages give none of the claimed 44%, 14%, or 2% proportions. Searches for those figures and for the urinary-recovery table did not yield the values needed to check the claim. (LLM, conf=0.69)
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- Authors
- van der Ven, A., Vree, T., van Ewijk‐Beneken Kolmer, E., Koopmans, P., & van der Meer, J.
- Affiliations
- Radboud University Medical Center (NL)
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 1995-06
- Volume
- 39
- Issue
- 6
- Pages
- 621-625
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC1365073
- OpenAlex
- W2067908267
- Cited by
- 45
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 1
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
- Keywords
- sulfamethoxazole, HIV infection, urinary excretion, drug metabolism, hydroxylamine metabolites, pharmacokinetics
- MeSH terms
- Adult, Dose-Response Relationship, Drug, Female, HIV Seropositivity, Humans, Male, Middle Aged, Sulfamethoxazole
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