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Polymorphic Acetylation of the Antibacterials, Sulfamethazine and Dapsone, in South Indian Subjects
A group of South Indian subjects was studied for their capacities to acetylate sulfamethazine (SMZ) and dapsone (DDS) and to clear DDS from the circulation. An apparent trimodal distribution of acetylator phenotypes was found in 49 subjects (51% slow, 12% intermediate, and 37% rapid acetylators) from measurements of the percentage acetylation of SMZ in 6-hour plasma samples after administration of 10 mg SMZ/kg. The intermediate phenotype was not discernible from either the percentage acetylation of SMZ in urine (collected concurrently with the plasma after SMZ) or that of DDS in plasma after the ingestion of 50 mg DDS by the same subjects. The latter two measurements yielded a biomdal distribution of 59% slow and 41% rapid acetylators, nearly identical to earlier reported distributions of isoniazid inactivator phenotypes in larger numbers of South Indian tuberculosis patients. In the current group, acetylation of DDS and SMZ was positively correlated. The half-time of disappearance (T½) of DDS, an expression of the rate of clearance from the plasma, ranged from 13 to 40 hours. No correlation was found between the subject's capacity to acetylate DDS and the T½ value for DDS. These results were generally consistent with earlier observations made during similar studies of American and Filipino subjects.
Author Notes
Present address: St. Catherine's Hospital, Church Road, Birkenhead, Merseyside, England.