caa a22 4500 397592442 CHVBK 20180308164942.0 cr unu---uuuuu 161202e199605 xx s 000 0 eng 10.1093/jac/37.suppl_B.55 doi (NATIONALLICENCE)oxford-10.1093/jac/37.suppl_B.55 Adverse reactions to co-trimoxazole in HIV infection: A reappraisal of the glutathione-hydroxylamine hypothesis [Elektronische Daten] [André J. A. M. van der Ven, Tom B. Vree, Peter P. Koopmans, Jos W. M. van der Meer] 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. © 1996 The British Society for Antimicrobial Chemotherapy Articles nationallicence van der Ven André J. A. M. Department of General Internal Medicine, Division of General Internal Medicine P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut Vree Tom B. Department of Clinical Pharmacy, Academic Hospital Nijmegen P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut Koopmans Peter P. Department of General Internal Medicine, Division of General Internal Medicine P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut van der Meer Jos W. M. Department of General Internal Medicine, Division of General Internal Medicine P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut Journal of Antimicrobial Chemotherapy Oxford University Press 37(1996-05), 55-60 0305-7453 37<55 1996 37 jac https://doi.org/10.1093/jac/37.suppl_B.55 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/37.suppl_B.55 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- van der Ven André J. A. M. Department of General Internal Medicine, Division of General Internal Medicine P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Vree Tom B. Department of Clinical Pharmacy, Academic Hospital Nijmegen P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Koopmans Peter P. Department of General Internal Medicine, Division of General Internal Medicine P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- van der Meer Jos W. M. Department of General Internal Medicine, Division of General Internal Medicine P.O. Box 9101, 6500 HB Nijmegen, The Netherlands aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 37(1996-05), 55-60 0305-7453 37<55 1996 37 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford