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- Title
Adverse reactions to co-trimoxazole in HIV infection: A reappraisal of the glutathione-hydroxylamine hypothesis.
- Authors
van der Ven, André J. A. M.; Vree, Tom B.; Koopmans, Peter P.; van der Meer, Jos W. M.
- Abstract
It is postulated that the unstable hydroxylamine metabolite of sulphamethoxazole is responsible for the adverse reactions to co-trimoxazole and in HIV infection systemic glutathione deficiency leads to a reduced capacity to counteract the hydroxylamine toxicity. This hypothesis has been investigated by studying the metabolism of sulphamethoxazole and assessing glutathione status in HIV infection in order to explore the modification of treatment. It is concluded that the toxicity of plasma sulphamethoxazole hydroxylamine is counteracted by normal glutathione concentrations as is the case in HIV-seropositive patients, but that increased oxidation within certain cells in HIV infected individuals may possibly give rise to increased concentrations of reactive intermediates of sulphamethoxazole.Sulphametrole and sulphamethoxazole have similar half-lives but are metabolized differently: in vivo no oxidised metabolites of sulphametrole could be detected. In a retrospective study the rate of adverse reactions to trimethoprim-sulphametrole appeared to be in the lower range of those reported for trimethoprim-sulphamethox-azole indicating that the combination of trimethoprim-sulphametrole may be more favourable. The ratio of trimethoprim:sulphonamide is 1:5, but in-vitro studies with Toxoplasma gondii indicate that because of the synergic effect of both agents the dose of sulphonamide is possibly unnecessarily high.
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 1996, Vol 37, Issue suppl_B, p55
- ISSN
0305-7453
- Publication type
Article
- DOI
10.1093/jac/37.suppl_B.55