Cytochrome P450-dependent toxicity of dapsone in human erythrocytes.

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Ganesan S, Sahu R, Walker LA, Tekwani BL

Cytochrome P450-dependent toxicity of dapsone in human erythrocytes.

J Appl Toxicol. 2010 Apr;30(3):271-5. doi: 10.1002/jat.1493.

PubMed ID

19998329 [ View in PubMed

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Abstract

The most prominent adverse effects seen during treatment with dapsone, an antibacterial and antiprotozoal agent, are hemolysis and methemoglobinemia. An in vitro microsomal/cytochrome P(450) (CYP)-linked assay, which allows reactive metabolites generated in situ to react with the co-incubated human erythrocytes, was employed to profile CYP isoforms responsible for hemotoxicity of dapsone. Dapsone caused a robust generation of methemoglobin in human erythrocytes in the presence of human/mouse liver microsomes, which indicates contribution of CYP-mediated metabolism for hemotoxicity. The highest methemoglobin formation with dapsone was observed with CYP2C19, with minor contributions from CYP2B6, CYP2D6 and CYP3A4. Cimetidine and chloramphenicol completely abrogated methemoglobin generation by dapsone, thus confirming a predominant contribution of CYP2C19. The results provide useful insights into CYP-dependent hemotoxicity of dapsone in human erythrocytes.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Dapsone	Cytochrome P450 2C19	Protein	Humans	Unknown	Substrate	Details