N-hydroxylamine Dapsone

N-hydroxylamine Dapsone is an active metabolite of dapsone .¹ It is formed via N-hydroxylation of dapsone by the cytochrome P450 (CYP) isoforms CYP2C8, CYP2C9, CYP2C18, and CYP2C19 in the liver.² N-hydroxylamine Dapsone is cytotoxic to rat hepatocytes (LC₅₀ = 3.6 mM).³ It induces hemolysis in isolated human erythrocytes at a concentration of 100 µM.¹ N-hydroxylamine Dapsone induces phosphatidylserine (PS) exposure on the outer membrane, a marker of apoptosis and platelet activation, and increases the production of reactive oxygen species (ROS) in a concentration-dependent manner in isolated human erythrocytes. It increases thrombus weight in a rat model of surgically induced thrombosis when administered at a single dose of 50 mg/kg or at a dose of 10 mg/kg per day for four days.

1.Bian, Y., Kim, K., An, G.-J., et al.Dapsone hydroxylamine, an active metabolite of dapsone, can promote the procoagulant activity of red blood cells and thrombosisToxicol. Sci.172(2)435-444(2019) 2.Winter, H.R., Wang, Y., and Unadkat, J.D.CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsoneDrug Metab. Dispos.28(8)865-868(2000) 3.Veggi, L.M., Pretto, L., Ochoa, E.J., et al.Dapsone induces oxidative stress and impairs antioxidant defenses in rat liverLife Sci.83(5-6)155-163(2008)