Administration Of Dapsone Research Articles

Agranulocytosis during Dapsone Administration

Fatal agranulocytosis developed during treatment of a patient with dermatitis herpetiformis. Although he received other medications, dapsone was considered the probable cause of the agranulocytosis. Recent reports have documented the occurrence of dapsone-induced agranulocytosis during malaria prophylaxis. The present case emphasizes the possibility of this serious and sometimes fatal complication arising during sulfone therapy of dermatologicdisorders.

The polymorphic acetylation of dapsone in man.

The characteristics of the acetylation of dapsone (avlosulfon) were found to parallel those of isoniazid and sulfamethazine in 19 subjects, thereby establishing the genetic polymorphism for the acetylation of dapsone. This polymorphism was revealed by the distribution of the ratios of the plasma concentration of acetylated to parent drug. The acetylation capacity for dapsone was shown to be a reproducible, individual characteristic. Acetylation of dapsone and deacetylation of monoacetyl dapsone occurred concurrently. Constant plasma ratios of acetylated to parent drug characteristic for the individual were attained immediately after administration of dapsone but only after several hours following administration of monoacetyl dapsone. The available data suggest that acetylation rather than deacetylation is the primary determinant of these ratios. Rates of disappearance of dapsone and monoacetyl dapsone from the plasma were the same regardless of which of the two was administered or of the acetylator phenotype of the subject. After dapsone, no differences between rapid and slow acetylators were found in the 24 hour urinary excretion of dapsone and its conjugates hydrolyzed by mild or strong acid treatment. Rapid acetylators excreted significantly more monoacetyl dapsone and its acidlabile conjugates than slow acetylators. Because these compounds accounted for only a very small fraction of the dose, it was not possible to phenotype individuals by these measurements. More dapsone and acid‐hydrolyzable conjugates of dapsone were found in 120 hour urine collections after monoacetyl dapsone than after dapsone in both phenotypes.

Death of Mycobacterium leprae in Mice, and the Additional Effect of Dapsone Administration

SummaryIf the assumptions be valid that the lag phase of bacterial multiplication is constant when M. leprae are repeatedly harvested from untreated mice and passed to other mice of the same inbred strain, and that those M. leprae capable of multiplying in the mouse foot pad do so always at the same rate, then the results of these experiments may be interpreted to show that once the peak of bacterial multiplication has been reached, death of M. leprae ensues. Death of M. leprae appears to have occurred in mice during DDS treatment at the same rate as in the untreated mice, but the lag phase of bacterial growth was uniformly prolonged as a result of treatment.