title: The effect of acetylation and deacetylation on the disposition of dapsone and monoacetyl dapsone hydroxylamines in human erythrocytes in-vitro.
abstract: The fates of both dapsone and monoacetyl hydroxylamine have been studied in terms of acetylation and deacetylation within the human erythrocyte in-vitro. A comparison between the two metabolites showed equipotency in methaemoglobin generation at 15 min, although the monoacetyl derivative was the more rapid haemoglobin oxidizer. Within the erythrocytes, both dapsone and monoacetyl hydroxylamines were found to undergo acetylation, deacetylation and diacetylation. Of the inhibitors of acetylation studied, folate caused an increase in methaemoglobin formation associated with both metabolites, which led to a rise in both acetylated and non-acetylated amine formation. Amethopterin was associated with a rise in hydroxylamine mediated methaemoglobin formation which coincided with a fall in acetylated products. It is possible that the hydroxylamines undergo erythrocytic processes of acetylation and deacetylation before methaemoglobin-mediated reduction to their respective amines.
authors.affiliation: Department of Pharmaceutical Sciences, Aston University, Birmingham, UK.
authors.forename: M D
authors.initials: MD
authors.lastname: Coleman
authors.forename: K K
authors.initials: KK
authors.lastname: Pahal
authors.forename: J M
authors.initials: JM
authors.lastname: Gardiner
mesh_terms: D000072:Acedapsone / Q000097:blood; D000107:Acetylation; D000328:Adult; D000588:Amines / Q000097:blood / Q000493:pharmacokinetics*; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003622:Dapsone / Q000097:blood / Q000493:pharmacokinetics*; D003640:Dealkylation; D004912:Erythrocytes / Q000378:metabolism*; D005492:Folic Acid / Q000494:pharmacology; D005493:Folic Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006397:Hematinics / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008706:Methemoglobin / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology
chemical_list: D000588:Amines; D000890:Anti-Infective Agents; D005493:Folic Acid Antagonists; D006397:Hematinics; D000072:Acedapsone; D003622:Dapsone; D008706:Methemoglobin; D005492:Folic Acid; D005947:Glucose; D008727:Methotrexate