Abstract:
:It has been suggested, on the basis of work in cell-free systems, that sulfonamide hydroxy-lamines are metabolized to nitroso metabolites which may be the proximate toxins mediating sulfonamide hypersensitivity reactions. We performed time-course experiments investigating the toxicity of the hydroxylamine and nitroso derivatives of sulfamethoxazole to investigate this hypothesis. The nitroso derivative of sulfamethoxazole was significantly more toxic than the hydroxylamine derivative (P < 0.05). When the LC50 was compared over time, there was a significant decrease in the LC50 of the hydroxylamine of sulfamethoxazole over time, while there was no change in the LC50 of the nitroso derivative. There was an equivalent reduction in toxicity demonstrated when the hydroxylamine or nitroso derivatives were co-incubated with glutathione. This supports the role of the nitroso as a proximate toxin mediating sulfonamide hypersensitivity reactions and suggests an explanation for the high rate of adverse reactions to sulfonamides among patients with AIDS.
journal_name
Toxicologyjournal_title
Toxicologyauthors
Rieder MJ,Krause R,Bird IAdoi
10.1016/0300-483x(94)02900-fsubject
Has Abstractpub_date
1995-01-06 00:00:00pages
141-6issue
1-3eissn
0300-483Xissn
1879-3185pii
0300-483X(94)02900-Fjournal_volume
95pub_type
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