32695-27-5Relevant academic research and scientific papers
Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo
Mitra, Ashoke K.,Thummel, Kenneth E.,Kalhorn, Thomas F.,Kharasch, Evan D.,Unadkat, Jashvant D.,Slattery, John T.
, p. 556 - 566 (1995)
Dapsone toxicity is putatively initiated by formation of a hydroxylamine metabolite by cytochromes P450. In human liver microsomes, the kinetics of P450-catalyzed N-oxidation of dapsone were biphasic, with the Michaelis-Menten constants of 0.14 ± 0.05 and 0.004 ± 0.003 mmol/L and the respective maximum velocities of 1.3 ± 0.1 and 0.13 ± 0.04 nmol/mg protein/min (mean ± SEM). Troleandomycin (40 μmol/L) inhibited hydroxylamine formation at 100 μmol/L dapsone by 50%; diethyldithiocarbamate (150 μmol/L) and tolbutamide (400 μmol/L) inhibited at 5 μmol/L dapsone by 50% and 20%, respectively, suggesting that the low-affinity isozyme is CYP3A4 and the high-affinity isozymes are 2E1 and 2C. Disulfiram, 500 mg, 18 hours before a 100 mg oral dose of dapsone in healthy volunteers, diminished area under the hydroxylamine plasma concentration-time curve by 65%, apparent formation clearance of the hydroxylamine by 71%, and clearance of dapsone by 26%. Disulfiram produced a 78% lower concentration of methemoglobin 8 hours after dapsone.
Reactive oxygen species generation and its role in the differential cytotoxicity of the arylhydroxylamine metabolites of sulfamethoxazole and dapsone in normal human epidermal keratinocytes
Vyas, Piyush M.,Roychowdhury, Sanjoy,Woster, Patrick M.,Svensson, Craig K.
, p. 275 - 286 (2007/10/03)
Cutaneous drug reactions (CDR) are responsible for numerous minor to life-threatening complications. Though the exact mechanism for CDR is not completely understood, evidence suggests that bioactivation of drugs to reactive oxygen or nitrogen species is a
