Metabolic Disposition of Dapsone in Patients with Dapsone-Resistant Leprosy *

Abstract
To investigate the question of whether dapsone (DDS) resistance in leprosy patients is related to the metabolic disposition of DDS, we studied a group of 22 patients who had relapsed with DDS-resistant disease after approximately 19 years of sulfone therapy. Tests for acetylator phenotype with sulfamethazine (SMZ) showed that this group of patients contained a lower percentage of slow and a higher percentage of intermediate and rapid acetylators than had been observed previously in other populations. Acetylation of SMZ and DDS were directly related. In addition, plasma clearance of DDS for the DDS-resistant group was significantly faster than that found previously in any other population. These observations suggest that the emergence of DDS resistance may be associated with the rapid or intermediate acetylator phenotype and an ability to clear DDS from the circulation at a fast rate. Combining the two parameters into a multirisk factor yielded a significantly higher mean value in DDS-resistant patients than that of any other group studied previously. The implications of these findings for the large-scale treatment of leprosy patients are discussed.

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