Pharmacokinetics of dapsone administered daily and weekly in human immunodeficiency virus-infected children

Although dapsone is a commonly used alternative agent for prophylaxis again st Pneumocystis carinii pneumonia in children intolerant to trimethoprim-su lfamethoxazole, there are few data that describe dapsone pharmacokinetics i n children. We studied dapsone pharmacokinetics in 30 children (median age, 2.8 years; age range, 0.3 to 12 years) receiving a new proprietary liquid preparation by three dosing regimens (1 mg/kg of body weight daily, 2 mg/kg daily, or 4 mg/kg weekly). Dosing of children with 2 mg/kg daily or 4 mg/k g weekly resulted in peak concentrations equivalent to those reached in adu lts receiving 100-mg tablets daily. For the entire population, the median h alf-life was 22.2 h (range, 7.1 to 40.3 h), the median oral clearance was 0 .0365 liter/kg/h (range, 0.0104 to 0.1021 liter/kg/h), and the median oral apparent volume of distribution was 1.13 liters/kg (range, 0.50 to 2.32 lit ers/kg). The median dapsone oral clearance was significantly increased in t hose infants less than 2 years of age compared to the oral clearance in tho se over 2 years of age (0.0484 versus 0.0278 liter/kg/h; P = 0.011). These data suggest that absorption of this liquid preparation is adequate and tha t the concentrations in the sera of children receiving 2 mg/kg daily or 4 m g/kg weekly are equivalent to those seen in adults receiving standard dapso ne dosing. Dapsone oral clearance appears to be increased in children under 2 years of age.