Metabolic disposition of dapsone in African leprosy patients

Abstract

In a preliminary study (Study 1) of 20 African leprosy patients receiving various doses of dapsone (DDS), the authors found a distribution of capacities to acetylate DDS that suggested the polymorphism of acetylation observed in other populations. A more detailed investigation (Study 2) in a subsequent group of 21 patients using sulfamethazine (SMZ) as the primary drug for determining acetylator phenotype as well as DDS clearly demonstrated that African patients exhibit the polymorphism of acetylation of these drugs. As in other populations studied previously, plasma clearance rates of DDS as expressed by the half-time of disappearance were unrelated to acetylator phenotype. Clearance rates or acetylation capacities were also unrelated to age, sex, or body weight of the patients, or to the dose of DDS administered per week. In 5 patients who participated in both Studies 1 and 2, no consistent marked differences in acetylation of DDS or plasma clearance rates of DDS were noted even though the two studies were separated by 11 months. A positive linear relationship between the 4-h level of DDS after the last dose and total dose of DDS per week was observed.