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The Disposition of the Antileprotic Drug Dapsone (DDS) in Philippine Subjects^*

A genetic polymorphism for acetylation of dapsone was demonstrated in 50 Philippine subjects native to the island of Cebu; a direct correlation was found between percentage acetylation of dapsone in plasma and of sulfamethazine in urine. Repeat studies with sulfamethazine in 32 of these subjects showed that the results from plasma and urinary assays were directly related, and that plasma assays gave a better differentiation of individuals into rapid and slow phenotypes. The high percentage (72%) of rapid acetylators is consistent with the Mongoloid origin of these Philippine subjects. Percentage acetylation of sulfamethazine was inversely related to plasma levels of this drug, and directly related to levels of N⁴-acetylsulfamethazine. Percentage acetylation of dapsone was directly related to plasma monoacetyldapsone levels, but was not related in any way to dapsone levels. No evidence for the presence of dapsone conjugates in plasma was found. Half-time of disappearance of either dapsone or monoacetyldapsone were not different in the two phenotypes and ranged from 14 to 53 hours in the entire group. Repeat studies in the six subjects showing the most divergent values confirmed the initial observations. The mean half-times were substantially higher than had been observed previously in American subjects.

Accepted for publication March 11, 1972.

^* Some of these data have been presented at the 5th Leprosy Research Conference, Boston, Mass., April 1970,¹ and at the fall meeting of the American Society of Pharmacology and Experimental Therapeutics, Palo Alto, California, August 1970.² Supported in part by the United States—Japan Cooperative Medical Science Program administered by the National Institute of Allergy and Infectious Diseases (Grant R22-AI-08214 and Contracts NIH-69-2003 and NIH-70-2283), National Institutes of Health, Department of Health, Education and Welfare.