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The Disposition of the Antileprotic Drug Dapsone (DDS) in Philippine Subjects
John H. Peters
John H. Peters
Life Sciences Division, Stanford Research Institute, Leonard Wood Memorial—Eversley Childs Sanatarium Leprosy Research Laboratory, Leprosy Research Unit, Public Health Service Hospital, Menlo Park, California 94025, Philippines
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G. Ross Gordon
G. Ross Gordon
Life Sciences Division, Stanford Research Institute, Leonard Wood Memorial—Eversley Childs Sanatarium Leprosy Research Laboratory, Leprosy Research Unit, Public Health Service Hospital, Menlo Park, California 94025, Philippines
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D. C. Ghoul
D. C. Ghoul
Life Sciences Division, Stanford Research Institute, Leonard Wood Memorial—Eversley Childs Sanatarium Leprosy Research Laboratory, Leprosy Research Unit, Public Health Service Hospital, Menlo Park, California 94025, Philippines
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J. G. Tolentino
J. G. Tolentino
Life Sciences Division, Stanford Research Institute, Leonard Wood Memorial—Eversley Childs Sanatarium Leprosy Research Laboratory, Leprosy Research Unit, Public Health Service Hospital, Menlo Park, California 94025, Philippines
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G. P. Walsh
G. P. Walsh
Life Sciences Division, Stanford Research Institute, Leonard Wood Memorial—Eversley Childs Sanatarium Leprosy Research Laboratory, Leprosy Research Unit, Public Health Service Hospital, Menlo Park, California 94025, Philippines
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Louis Levy
Louis Levy
Life Sciences Division, Stanford Research Institute, Leonard Wood Memorial—Eversley Childs Sanatarium Leprosy Research Laboratory, Leprosy Research Unit, Public Health Service Hospital, Menlo Park, California 94025, Philippines
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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.
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