Reactions of the nitroso and hydroxylamine metabolites of sulfamethoxazole with reduced glutathione. Implications for idiosyncratic toxicity
Abstract
N4-oxidation of sulfonamides has been implicated in the pathogenesis of idiosyncratic reactions to these antimicrobials. In vitro toxicity assays employing mononuclear leukocytes as target cells have shown that the toxicity of sulfamethoxazole hydroxylamine (SMX-HA) is inhibited by exogenous glutathione, suggesting that conjugation with glutathione is an important detoxification pathway. However, in these experiments, significant depletion of cellular glutathione only occurred at concentrations of SMX-HA greater than or equal to 300 microM. At concentrations of SMX-HA which produce 50% toxicity in mononuclear leukocytes (approximately 100 microM), there was not a significant loss of glutathione. SMX-HA also caused a small but significant increase in oxidized glutathione concentrations. In cell-free experiments, reduced glutathione (GSH) prevented the autooxidation of SMX-HA to nitrososulfamethoxazole (nitroso-SMX). During this process, oxidized glutathione was formed. GSH rapidly reacted with nitroso-SMX to form a labile semimercaptal conjugate. Physiologically relevant concentrations of GSH (i.e. 1 mM) favored thiolytic cleavage of the semimercaptal to form SMX-HA. Isomerization of the semimercaptal to the more stable sulfinamide occurred at low GSH concentrations. Purified glutathione transferases had no effect on the reaction of SMX-HA with GSH. Therefore, glutathione is important in protecting cells from the toxicity of SMX-HA largely by preventing its further oxidation to nitroso-SMX. Stable glutathione conjugates are likely to be formed only in small quantities under physiological conditions. Conjugation with glutathione would not be expected to be a major pathway for clearance of the hydroxylamine and nitroso metabolites of sulfonamides.
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SMX-HA can undergo further auto-oxidation to form the reactive metabolite SMX-NO, which has been linked to protein binding and hypersensitivity reactions.
“SMX-HA can then undergo further auto-oxidation to form the reactive metabolite, sulfamethoxazole-nitroso (SMX-NO), which has been linked to protein binding and hypersensitivity reactions.15–17”
From N-Acetyltransferase (NAT) 1 and NAT2 Enzyme Activities Drive Interindividual Variability in Sulfamethoxazole N-Acetylation (2025) · cites this paper as [15]
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Stepan, A. F., Walker, D. P., Bauman, J. N., Price, D. A., Baillie, T. A., Kalgutkar, A. S. S., & Aleo, M. D. (2011) · Chemical Research in Toxicology · doi:10.1021/tx200168d · Cited by 711 · see citing works
Svensson, C. K., Cowen, E. W., & Gaspari, A. A. (2001) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01501-1 · Cited by 274 · see citing works
Immune pathomechanism of drug hypersensitivity reactions
Pichler, W. J., Naisbitt, D. J., & Park, B. K. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.11.048 · Cited by 186 · see citing works
Deleterious Effects of Reactive Metabolites
Attia, S. M. (2010) · Oxidative Medicine and Cellular Longevity · doi:10.4161/oxim.3.4.13246 · Cited by 175 · see citing works
The danger hypothesis—potential role in idiosyncratic drug reactions
Pirmohamed, M., Naisbitt, D. J., Gordon, F., & Park, B. K. (2002) · Toxicology · doi:10.1016/s0300-483x(02)00255-x · Cited by 164 · see citing works
Mechanisms of NSAID-Induced Hepatotoxicity
Boelsterli, U. A. (2002) · Drug Safety · doi:10.2165/00002018-200225090-00003 · Cited by 164 · see citing works
Reilly, T. P., Lash, L. H., Doll, M. A., Hein, D. W., Woster, P. M., & Svensson, C. K. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00985.x · Cited by 150 · see citing works
Naisbitt, D. J., Farrell, J., Gordon, S. F., Maggs, J. L., Burkhart, C., Pichler, W. J., Pirmohamed, M., & Park, B. K. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.3.628 · Cited by 141 · see citing works
Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity
Naisbitt, D. J., Hough, S. J., Gill, H., Pirmohamed, M., Kitteringham, N. R., & Park, B. K. (1999) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702453 · Cited by 134 · see citing works
Idiosyncratic toxicity associated with potentiated sulfonamides in the dog
Trepanier, L. A. (2004) · Journal of Veterinary Pharmacology and Therapeutics · doi:10.1111/j.1365-2885.2004.00576.x · Cited by 134 · see citing works
Naisbitt, D. J., Gordon, S. F., Pirmohamed, M., Burkhart, C., Cribb, A. E., Pichler, W. J., & Park, B. K. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704074 · Cited by 133 · see citing works
The Biochemistry of Drug Metabolism – An Introduction
Testa, B., & Krämer, S. D. (2008) · Chemistry & Biodiversity · doi:10.1002/cbdv.200890199 · Cited by 132 · see citing works
Advances in molecular toxicology–towards understanding idiosyncratic drug toxicity
Park, B. K., Kitteringham, N. R., Powell, H., & Pirmohamed, M. (2000) · Toxicology · doi:10.1016/s0300-483x(00)00303-6 · Cited by 129 · see citing works
Sanderson, J. P., Naisbitt, D. J., Farrell, J., Ashby, C. A., TUCKER, M., Rieder, M. J., Pirmohamed, M., Clarke, S. E., & Park, B. K. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5533 · Cited by 123 · see citing works
Metabolic activation in drug allergies
Park, B. K., Naisbitt, D. J., Gordon, S. F., Kitteringham, N. R., & Pirmohamed, M. (2001) · Toxicology · doi:10.1016/s0300-483x(00)00397-8 · Cited by 122 · see citing works
Should Celecoxib Be Contraindicated in Patients Who Are Allergic to Sulfonamides?
Knowles, S. R., Shapiro, L. E., & Shear, N. H. (2001) · Drug Safety · doi:10.2165/00002018-200124040-00001 · Cited by 117 · see citing works
In vitroanalysis of metabolic predisposition to drug hypersensitivity reactions
Riley, R. J., & Leeder, J. S. (1995) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.1995.tb03463.x · Cited by 114 · see citing works
Kalgutkar, A. S. S., & Didiuk, M. T. (2009) · Chemistry & Biodiversity · doi:10.1002/cbdv.200900055 · Cited by 103 · see citing works
Allergic adverse reactions to sulfonamides
Choquet‐Kastylevsky, G., Vial, T., & Descotes, J. (2002) · Current Allergy and Asthma Reports · doi:10.1007/s11882-002-0033-y · Cited by 102 · see citing works
Drug bioactivation and protein adduct formation in the pathogenesis of drug-induced toxicity
Park, B. K., Laverty, H., Srivastava, A., Antoine, D. J., Naisbitt, D. J., & Williams, D. P. (2010) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.09.011 · Cited by 102 · see citing works
Candidate HLA genes for prediction of co-trimoxazole-induced severe cutaneous reactions
Kongpan, T., Mahasirimongkol, S., Konyoung, P., Kanjanawart, S., Chumworathayi, P., Wichukchinda, N., Kidkeukarun, R., Preechakul, S., Khunarkornsiri, U., Bamrungram, W., et al. (2015) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000153 · Cited by 95 · see citing works
Burkhart, C., von Greyerz, S., Depta, J. P. H., Naisbitt, D. J., Britschgi, M., Park, K. B., & Pichler, W. J. (2001) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0703845 · Cited by 95 · see citing works
Comparison of the In Vitro Cytotoxicity of Hydroxylamine Metabolites of Sulfamethoxazole and Dapsone
Reilly, T. P., Bellevue, F. H., Woster, P. M., & Svensson, C. K. (1998) · Biochemical Pharmacology · doi:10.1016/s0006-2952(97)00547-9 · Cited by 90 · see citing works
Visentin, M., Lenggenhager, D. M., Gai, Z., & Kullak-Ublick, G. A. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2017.08.033 · Cited by 88 · see citing works
The Generation, Detection, and Effects of Reactive Drug Metabolites
Stachulski, A. V., Baillie, T. A., Park, B. K., Obach, R. S., Dalvie, D., Williams, D. P., Srivastava, A., Regan, S., Antoine, D. J., Goldring, C. E., et al. (2012) · Medicinal Research Reviews · doi:10.1002/med.21273 · Cited by 88 · see citing works
Sulfonamide Hypersensitivity: Fact and Fiction
Khan, D. A., Knowles, S. R., & Shear, N. H. (2019) · The Journal of Allergy and Clinical Immunology In Practice · doi:10.1016/j.jaip.2019.05.034 · Cited by 87 · see citing works
The Role of Active Metabolites in Drug Toxicity
Pirmohamed, M., Kitteringham, N. R., & Park, B. K. (1994) · Drug Safety · doi:10.2165/00002018-199411020-00006 · Cited by 86 · see citing works
Callan, H. E., Jenkins, R. E., Maggs, J. L., Lavergne, S. N., Clarke, S. E., Naisbitt, D. J., & Park, B. K. (2009) · Chemical Research in Toxicology · doi:10.1021/tx900034r · Cited by 84 · see citing works
N-acetyltransferases: Pharmacogenetics and clinical consequences of polymorphic drug metabolism
Spielberg, S. P. (1996) · Journal of Pharmacokinetics and Biopharmaceutics · doi:10.1007/bf02353477 · Cited by 81 · see citing works
Metabolism of sulfamethoxazole in Arabidopsis thaliana cells and cucumber seedlings
Dudley, S., Sun, C., Jiang, J., & Gan, J. J. (2018) · Environmental Pollution · doi:10.1016/j.envpol.2018.07.094 · Cited by 76 · see citing works
Chemical toxicology: reactive intermediates and their role in pharmacology and toxicology
Erve, J. C. L. (2006) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2.6.923 · Cited by 74 · see citing works
Farrell, J., Naisbitt, D. J., Drummond, N. S., Depta, J. P. H., Vilar, F. J., Pirmohamed, M., & Park, B. K. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.050112 · Cited by 74 · see citing works
Mechanism of bioactivation and covalent binding of 2,4,6-trinitrotoluene
Leung, K., Yao, M., Stearns, R. A., & Chiu, S. L. (1995) · Chemico-Biological Interactions · doi:10.1016/0009-2797(94)03606-9 · Cited by 73 · see citing works
Drug metabolism, danger signals, and drug-induced hypersensitivity
Gruchalla, R. S. (2001) · Journal of Allergy and Clinical Immunology · doi:10.1067/mai.2001.118509 · Cited by 73 · see citing works
Reactive metabolites and their role in drug reactions
Naisbitt, D. J., Williams, D. P., Pirmohamed, M., Kitteringham, N. R., & Park, B. K. (2001) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/00130832-200108000-00007 · Cited by 69 · see citing works
Haptenation of Sulfonamide Reactive Metabolites to Cellular Proteins
Manchanda, T., Hess, D. A., Dale, L., Ferguson, S. S. G., & Rieder, M. J. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.5.1011 · Cited by 69 · see citing works
The Relationship Between the Disposition and Immunogenicity of Sulfamethoxazole in the Rat
Gill, H., Hough, S. J., Naisbitt, D. J., Maggs, J. L., Kitteringham, N. R., Pirmohamed, M., & Park, B. K. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36867-3 · Cited by 69 · see citing works
Naisbitt, D. J., O’Neill, P. M., Pirmohamed, M., & Park, B. K. (1996) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(96)00260-0 · Cited by 67 · see citing works
Pharmacogenetics of Adverse Drug Reactions
Osanlou, O., Pirmohamed, M., & Daly, A. K. (2018) · Advances in pharmacology · doi:10.1016/bs.apha.2018.03.002 · Cited by 67 · see citing works
Elsheikh, A., Lavergne, S. N., Castrejón-Flores, J. L., Farrell, J., Wang, H., Sathish, J. G., Pichler, W. J., Park, B. K., & Naisbitt, D. J. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000889 · Cited by 62 · see citing works
Role of bioactivation in drug-induced hypersensitivity reactions
Sanderson, J. P., Naisbitt, D. J., & Park, B. K. (2006) · The AAPS Journal · doi:10.1208/aapsj080107 · Cited by 61 · see citing works
Toxicophores: groups and metabolic routes associated with increased safety risk.
Williams, D. P., & Naisbitt, D. J. (2002) · PubMed · Cited by 62 · see citing works
Alfirevic, A., Stalford, A. C., Vilar, F. J., Wilkins, E., Park, B. K., & Pirmohamed, M. (2003) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.2003.01754.x · Cited by 62 · see citing works
Vyas, P. M., Roychowdhury, S., Woster, P. M., & Svensson, C. K. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2005.04.023 · Cited by 61 · see citing works
Kalish, R. S., LaPorte, A., Wood, J. A., & Johnson, K. L. (1994) · Journal of Allergy and Clinical Immunology · doi:10.1016/0091-6749(94)90202-x · Cited by 60 · see citing works
The importance of hapten–protein complex formation in the development of drug allergy
Faulkner, L., Meng, X., Park, B. K., & Naisbitt, D. J. (2014) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000000078 · Cited by 57 · see citing works
Reilly, T., Woster, P. M., & Svensson, C. K. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38046-2 · Cited by 57 · see citing works
Immediate‐type hypersensitivity drug reactions
Stone, S. F., Phillips, E. J., Wiese, M. D., Heddle, R. J., & Brown, S. G. A. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12297 · Cited by 53 · see citing works
Roychowdhury, S., Vyas, P. M., Reilly, T. P., Gaspari, A. A., & Svensson, C. K. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.086009 · Cited by 54 · see citing works
Lavergne, S. N., Wang, H., Callan, H., Park, B. K., & Naisbitt, D. J. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.155374 · Cited by 51 · see citing works
van der Ven, A., Mantel, M., Vree, T. B., Koopmans, P., & van der Meer, J. (1994) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1994.tb04339.x · Cited by 52 · see citing works
Eyer, P. (1994) · Environmental Health Perspectives · doi:10.1289/ehp.94102s6123 · Cited by 51 · see citing works
Elsheikh, A., Castrejón-Flores, J. L., Lavergne, S. N., Whitaker, P., Monshi, M. M., Callan, H., El-Ghaiesh, S. H., Farrell, J., Pichler, W. J., Peckham, D. G., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2010.12.1119 · Cited by 46 · see citing works
Specific polyclonal-based immunoassays for sulfathiazole
Pastor-Navarro, N., Garc�a-Bover, C., Maquieira, �., & Puchades, R. (2004) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-004-2683-1 · Cited by 47 · see citing works
Cribb, A. E., Pohl, L. R., Spielberg, S. P., & Leeder, J. S. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36874-0 · Cited by 46 · see citing works
van der Ven, A., Vree, T., van Ewijk‐Beneken Kolmer, E., Koopmans, P., & van der Meer, J. (1995) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1995.tb05721.x · Cited by 45 · see citing works
Safety of Celecoxib in Individuals Allergic to Sulfonamide
Shapiro, L. E., Knowles, S. R., Weber, E., Neuman, M. G., & Shear, N. H. (2003) · Drug Safety · doi:10.2165/00002018-200326030-00004 · Cited by 45 · see citing works
Mechanisms of drug reactions: The metabolic track
Shapiro, L. E., & Shear, N. H. (1996) · Seminars in Cutaneous Medicine and Surgery · doi:10.1016/s1085-5629(96)80034-4 · Cited by 45 · see citing works
Idiosyncratic Drug Hepatotoxicity Revisited: New Insights from Mechanistic Toxicology
Boelsterli, U. A. (2003) · Toxicology Mechanisms and Methods · doi:10.1080/15376510309824 · Cited by 44 · see citing works
Wang, D., Curtis, A., Papp, A. C., Koletar, S. L., & Para, M. F. (2012) · BMC Medical Genomics · doi:10.1186/1755-8794-5-32 · Cited by 42 · see citing works
Summan, M., & Cribb, A. E. (2002) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(02)00060-1 · Cited by 42 · see citing works
Time-course of toxicity of reactive sulfonamide metabolites
Rieder, M. J., Krause, R. S., & Bird, I. A. (1995) · Toxicology · doi:10.1016/0300-483x(94)02900-f · Cited by 42 · see citing works
Wolkenstein, P., Loriot, M., Aractingi, S., Cabelguenne, A., Beaune, P. H., & Chosidow, O. (2000) · Pharmacogenetics · doi:10.1097/00008571-200012000-00007 · Cited by 41 · see citing works
Neuman, M. G., Malkiewicz, I. M., Phillips, E. J., Rachlis, A., Ong, D., Yeung, E., & Shear, N. H. (2002) · Therapeutic Drug Monitoring · doi:10.1097/00007691-200212000-00008 · Cited by 40 · see citing works
Mitra, A., Thummel, K. E., Kalhorn, T. F., Kharasch, E. D., Unadkat, J. D., & Slattery, J. T. (1996) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(96)80011-7 · Cited by 40 · see citing works
Dorn, J. M., Alpern, M. L., McNulty, C. M. G., & Volcheck, G. W. (2018) · Current Allergy and Asthma Reports · doi:10.1007/s11882-018-0791-9 · Cited by 36 · see citing works
Nakayama, S., Takakusa, H., Watanabe, A., Miyaji, Y., Suzuki, W., Sugiyama, D., Shiosakai, K., Honda, K., Okudaira, N., Izumi, T., et al. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.111.039180 · Cited by 36 · see citing works
Cheng, L., Stewart, B. J. R., You, Q., Petersen, D. R., Ware, J. A., Piccotti, J. R., Kawabata, T. T., & Ju, C. (2008) · Molecular Pharmacology · doi:10.1124/mol.107.043273 · Cited by 34 · see citing works
Soejima, M., Sugiura, T., Kawaguchi, Y., Kawamoto, M., Katsumata, Y., Takagi, K., Nakajima, A., Mitamura, T., Mimori, A., Hara, M., et al. (2007) · Arthritis Research & Therapy · doi:10.1186/ar2134 · Cited by 34 · see citing works
Lavergne, S. N., Kurian, J. R., Bajad, S. U., Maki, J. E., Yoder, A. R., Guzinski, M. V., Graziano, F. M., & Trepanier, L. A. (2006) · Toxicology · doi:10.1016/j.tox.2006.01.018 · Cited by 32 · see citing works
Toxicophores, reactive metabolites and drug safety: when is it a cause for concern?
Kalgutkar, A. S. S., Fate, G. D., Didiuk, M. T., & Bauman, J. N. (2008) · Expert Review of Clinical Pharmacology · doi:10.1586/17512433.1.4.515 · Cited by 32 · see citing works
Recognition of Local Anesthetics by αβ+ T Cells
Zanni, M. P., von Greyerz, S., Hari, Y., Schnyder, B., & Pichler, W. J. (1999) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1999.00484.x · Cited by 32 · see citing works
Ott, G., Plitzko, B., Krischkowski, C., Reichmann, D., Bittner, F., Mendel, R. R., Kunze, T., Clement, B., & Havemeyer, A. (2014) · Chemical Research in Toxicology · doi:10.1021/tx500174u · Cited by 31 · see citing works
Role of Oxidative Stress in Hypersensitivity Reactions to Sulfonamides
Elzagallaai, A. A., Sultan, E. A., Bend, J. R., Abuzgaia, A. M., Loubani, E., & Rieder, M. J. (2019) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1535 · Cited by 31 · see citing works
Trepanier, L. A., Yoder, A. R., Bajad, S. U., Beckwith, M. D., Bellehumeur, J. L., & Graziano, F. M. (2004) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/00126334-200408150-00007 · Cited by 31 · see citing works
Lin, D., TUCKER, M., & Rieder, M. J. (2006) · Annals of Pharmacotherapy · doi:10.1345/aph.1g525 · Cited by 31 · see citing works
Immunopathogenesis of hypersensitivity syndrome reactions to sulfonamides
Neuman, M. G., Shear, N. H., Malkiewicz, I. M., Taeri, M., Shapiro, L. E., Krivoy, N., Haber, J. A., Gómez, M., Fish, J. S., Cartotto, R. C., et al. (2007) · Translational research · doi:10.1016/j.trsl.2006.12.001 · Cited by 31 · see citing works
Castrejón-Flores, J. L., Lavergne, S. N., El-Sheikh, A., Farrell, J., Maggs, J. L., Sabbani, S., O’Neill, P. M., Park, B. K., & Naisbitt, D. J. (2009) · Chemical Research in Toxicology · doi:10.1021/tx900329b · Cited by 29 · see citing works
Ogese, M. O., Jenkins, R. E., Maggs, J. L., Meng, X., Whitaker, P., Peckham, D. G., Faulkner, L., Park, B. K., & Naisbitt, D. J. (2014) · Chemical Research in Toxicology · doi:10.1021/tx500458k · Cited by 29 · see citing works
Sacco, J., Abouraya, M., Motsinger‐Reif, A. A., Yale, S. H., McCarty, C. A., & Trepanier, L. A. (2012) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e328357a735 · Cited by 27 · see citing works
Toxicogenetics in drug development
Park, B. K., & Pirmohamed, M. (2001) · Toxicology Letters · doi:10.1016/s0378-4274(01)00280-6 · Cited by 27 · see citing works
Kalgutkar, A. S. S. (2010) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.09.003 · Cited by 25 · see citing works
Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver
Veggi, L. M., Pretto, L., Ochoa, E. J., Catania, V. A., Luquita, M. G., Taborda, D. R., Pozzi, E. J. S., Ikushiro, S., Coleman, M. D., Roma, M. G., et al. (2008) · Life Sciences · doi:10.1016/j.lfs.2008.05.016 · Cited by 25 · see citing works
N-acetyltransferase: the practical consequences of polymorphic activity in man
Mitchell, S. C. (2019) · Xenobiotica · doi:10.1080/00498254.2019.1618511 · Cited by 24 · see citing works
Influence ofNAT2Polymorphisms on Sulfamethoxazole Pharmacokinetics in Renal Transplant Recipients
Kagaya, H., Miura, M., Niioka, T., Saito, M., Numakura, K., Habuchi, T., & Satoh, S. (2011) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.05037-11 · Cited by 23 · see citing works
Aerobic 2- and 4-nitroreduction of CB 1954 by human liver
Tang, M. H. Y., Helsby, N. A., Wilson, W. R., & Tingle, M. D. (2005) · Toxicology · doi:10.1016/j.tox.2005.07.021 · Cited by 23 · see citing works
Thomson, C. A., & Sporns, P. (1995) · Journal of Food Science · doi:10.1111/j.1365-2621.1995.tb05683.x · Cited by 22 · see citing works
Novel Clinical Biomarkers for Drug-Induced Liver Injury
Chen, Y., Guan, S., Guan, Y., Tang, S., Zhou, Y., Wang, X., Bi, H., & Huang, M. (2021) · Drug Metabolism and Disposition · doi:10.1124/dmd.121.000732 · Cited by 21 · see citing works
Adverse Drug Reactions: Mechanisms and Assessment
Ring, J., & Brockow, K. (2002) · European Surgical Research · doi:10.1159/000048905 · Cited by 21 · see citing works
Immunological principles of T-cell-mediated adverse drug reactions in skin
Naisbitt, D. J., Pirmohamed, M., & Park, B. K. (2007) · Expert Opinion on Drug Safety · doi:10.1517/14740338.6.2.109 · Cited by 19 · see citing works
Induction of delayed-type hypersensitivity to sulfamethoxazole in mice: role of metabolites
Choquet‐Kastylevsky, G., Santolaria, N., Tédone, R., Aujoulat, M., & Descotes, J. (2001) · Toxicology Letters · doi:10.1016/s0378-4274(00)00313-1 · Cited by 19 · see citing works
Vree, T. B., van der Ven, A. J. A. M., Koopmans, P. P., van Ewijk-Beneken Kolmer, E. W. J., & Verwey-van Wissen, C. P. W. G. M. (1995) · Clinical Drug Investigation · doi:10.2165/00044011-199509010-00008 · Cited by 18 · see citing works
Metabolic Disposition and Elimination of Tritum-Labeled Sulfamethoxazole in Pigs, Chickens and Rats
Guo, J., Sun, Y., Zhao, Y., Huang, L., Peng, D., Hao, H., Tao, Y., Chen, D., Cheng, G., Wang, X., et al. (2022) · Metabolites · doi:10.3390/metabo13010057 · Cited by 18 · see citing works
Diagnosis of allergic reactions to sulfonamides
Gruchalla, R. S. (1999) · Allergy · doi:10.1111/j.1398-9995.1999.tb04745.x · Cited by 18 · see citing works
Are drug metabolites able to cause T-cell-mediated hypersensitivity reactions?
Sullivan, A. K., Gibson, A., Park, B. K., & Naisbitt, D. J. (2014) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2015.992780 · Cited by 17 · see citing works
Baldo, B. A. (2014) · Antibodies · doi:10.3390/antib3010056 · Cited by 16 · see citing works
HOPKINS, J., Naisbitt, D. J., HUMPHREYS, N., Dearman, R. J., Kimber, I., & PARK, B. (2004) · Toxicology · doi:10.1016/j.tox.2004.08.010 · Cited by 16 · see citing works
Immunochemical Approaches to the Detection of Sulfathiazole in Animal Tissues
Lee, N. A., Holtzapple, C. K., Muldoon, M. T., Deshpande, S. S., & Stanker, L. H. (2001) · Food and Agricultural Immunology · doi:10.1080/09540100051074149 · Cited by 15 · see citing works
Nakkam, N., Saksit, N., Konyoung, P., Amornpinyo, W., Khunarkornsiri, U., Purimart, D., Pattanacheewapull, O., Naewla, T., Wattanachai, P., Khaeso, K., et al. (2022) · Drug Metabolism and Pharmacokinetics · doi:10.1016/j.dmpk.2022.100480 · Cited by 14 · see citing works
Hess, D. A., O'Leary, E. F., Lee, J. T., Almawi, W. Y., Madrenas, J., & Rieder, M. J. (2001) · The FASEB Journal · doi:10.1096/fj.00-0583fje · Cited by 14 · see citing works
- Authors
- Cribb, A. E., Miller, M., Leeder, J. S., Hill, J., & Spielberg, S. P.
- Affiliations
- University of Toronto (CA)
- Venue
- Drug Metabolism and Disposition
- Publisher
- Elsevier BV
- Published
- 1991-09
- Volume
- 19
- Issue
- 5
- Pages
- 900-906
- ISSN
- 0090-9556 (ISSN-L)
- OpenAlex
- W1790339004
- Cited by
- 155
- References
- 0
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 7 · 2017: 5 · 2016: 1 · 2015: 2 · 2014: 7 · 2013: 5 · 2012: 7
- FWCI
- 2.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Metabolism and Disposition (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Topics
- Health Sciences › Medicine › Pharmacology › Drug-Induced Adverse Reactions
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
- Keywords
- sulfamethoxazole, reduced glutathione, glutathione conjugation, idiosyncratic drug toxicity, mononuclear leukocytes, glutathione depletion, glutathione disulfide, glutathione S-transferase, drug detoxification
- MeSH terms
- Cell-Free System, Glutathione, Glutathione Reductase, Humans, Leukocytes, Mononuclear, Inactivation, Metabolic, Oxidation-Reduction, Sulfamethoxazole, In Vitro Techniques
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