Dapsone-induced hematologic toxicity: comparison of the methemoglobin-forming ability of hydroxylamine metabolites of dapsone in rat and human blood

Toxicology and Applied Pharmacology
C VageC K Svensson

Abstract

The relative methemoglobin (MetHgb) forming ability of two metabolites of dapsone, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine (MADDS-NOH), were compared in rat and human whole blood. Concentration-response curves for the two metabolites were generated in vitro in whole blood. Data were fit to both the Emax and Sigmoid Emax models. The Emax values for MetHgb formation in rat blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 83 (8) and 84 (2)%, while the EC50 values were 1087 (283) and 828 (104) microM, respectively (mean +/- SD). Neither these values nor those generated for the Sigmoid Emax model differed significantly between the two metabolites. Similarly, the Emax values in human blood for MADDS-NOH and DDS-NOH fitted to the Emax model were 79 (5) and 80 (2)%, while the EC50 values were 90 (17) and 95 (19) microM, respectively. These values also did not differ between the two metabolites using either pharmacodynamic model. MetHgb was produced at the same rate, reached similar peak concentrations, and exhibited the same rate of decline with both metabolites. The area under the MetHgb content versus time curve did not differ between the two metabolites. These data demonstrate that MADDS-NOH ...Continue Reading

Citations

Dec 10, 2009·Journal of Applied Toxicology : JAT·Shobana GanesanBabu L Tekwani
Mar 4, 2006·Archives of Medical Research·Shahin ShadniaMohammad Abdollahi
Oct 4, 2005·Clinica Chimica Acta; International Journal of Clinical Chemistry·Xiao-Xia YangShu-Feng Zhou
Apr 21, 2006·Biochemical Pharmacology·Daniela GiustariniRanieri Rossi
Mar 24, 2005·The Journal of Pharmacology and Experimental Therapeutics·Sanjoy RoychowdhuryCraig K Svensson

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