Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro

Cytochrome P450‐dependent toxicity of dapsone in human erythrocytes

“…Cimetidine has been shown to reduce the toxic eff ects of dapsone and improve its therapeutic eff ect in an earlier in vivo study (Rhodes et al, 1995). Several studies have shown that dapsone hydroxylamine could undergo spontaneous auto-oxidation to more-reactive arylnitroso derivatives which are reduced back to dapsone hydroxylamine by intracellular GSH, thus leading to long half-life of hemotoxic metabolite of dapsone (Coleman and Jacobus, 1993). Dapsone causes hemolysis in both normal and G6PD(−) populations and the mechanisms seem to involve drug-induced changes to erythrocyte membrane.…”

“…Hemolytic anemia and methemoglobinemia are well known dose-limiting hemotoxic eff ects of dapsone (Wilson and Harris, 1977). Metabolites of dapsone generated in the liver have been believed to be responsible for hemotoxic reactions (Cucinell et al, 1972;Coleman and Jacobus, 1993;Mitra et al, 1995). The N-hydroxy metabolites dapsone hydroxylamine and monoacetyl hydroxylamine have been investigated as the predominant hemolytic metabolites (Halmekoski et al, 1978;.…”

Hydroxylamines and Oximes: Biological Properties and Potential Uses as Therapeutic Agents

“…It turns out that the methemoglobin formed within the erythrocytes regenerates the parent drug, dapsone, from dapsone-HA, thereby recycling the drug for a fresh round of conversion of hemoglobin to methemoglobin 73 . The overall effect anticipated is an increase in the half-life of dapsone in vivo.…”

Potencialização do efeito metemoglobinizante da dapsona em ratos pela N-acetilcisteína

“…Outro uso da dapsona se dá em situações inflamatórias como na dermatite herpetiforme (Coleman, Jacobus, 1993). O uso deste medicamento, porém, é freqüentemente limitado, devido aos seus efeitos adversos.…”