The relationship between dapsone dose, serum concentration and disease severity in dermatitis herpetiformis.
20 patients with dermatitis herpetiformis maintained on once daily dosing of dapsone were studied to investigate the pharmacodynamics of dapsone in suppressing clinical disease. Multiple correlation analysis was performed on variables including dosage requirements, serum concentration of dapsone and monoacetyl dapsone, acetylation ratio, IgA-containing circulating immune complexes, adherence to a gluten-free diet, and clinical disease severity. It was found that: 1. dapsone exhibits good bioavailability in dermatitis herpetiformis with absorption being unaffected by presumed gluten-sensitive enteropathy; 2. there is wide variation in serum concentrations of dapsone and monoacetyl dapsone with no specific "therapeutic level"; 3. acetylator phenotype was unrelated to dapsone dose requirement; 4. serum dapsone concentration had only a weak correlation with disease severity; and 5. there was poor correlation between IgA circulating immune complexes and dapsone serum concentration. The use of daily dapsone dose requirements or dapsone serum concentration necessary for disease suppression as an indicator of disease severity in the research setting is inappropriate. Measurements of serum concentration of the parent drug (dapsone) or principal metabolite (monoacetyl dapsone) do not serve as a useful guide to therapeutic management.
D000107:Acetylation; D000936:Antigen-Antibody Complex / Q000032:analysis; D001682:Biological Availability; D003622:Dapsone / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D003874:Dermatitis Herpetiformis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004044:Dietary Proteins / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005983:Glutens / Q000008:administration & dosage; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D010641:Phenotype
D000936:Antigen-Antibody Complex; D004044:Dietary Proteins; D007070:Immunoglobulin A; D005983:Glutens; D003622:Dapsone; C018965:monoacetyldapsone