PHASE-I SAFETY AND PHARMACOKINETICS STUDY OF MICRONIZED ATOVAQUONE INHUMAN IMMUNODEFICIENCY VIRUS-INFECTED INFANTS AND CHILDREN

A phase I dose-escalating safety and pharmacokinetic study evaluated a n oral suspension of micronized atovaquone (m-atovaquone) in infants a nd children stratified into age groups from 1 month to 12 years of age . Dosages of 10, 30, and 45 mg/kg of body, weight/day were evaluated a s single daily doses over a period of 12 days. Steady-state concentrat ions in plasma were determined on day 12, and single postdose concentr ations were measured on days 1, 3, 5, 7, 9, 13, 15, 18, 21, and 24, Pr ior studies with adults suggest that the average plasma atovaquone con centration of 15 mu g/ml is associated with therapeutic success in mor e than 95% of patients with Pneumocystis carinii pneumonitis. The resu lts showed m-atovaquone to be safe and well tolerated. Dosages of 30 m g/kg/day were adequate to achieve an average steady-state concentratio n of greater than 15 mu g/ml in children ages 1 to 3 months and 2 to 1 2 gears, but a dosage of 45 mg/kg/day was needed to reach this concent ration in infants 3 to 24 months of age. The oral suspension of atovaq uone is safe and well tolerated in children. A single daily dose of 30 mg/kg provides bioavailability considered adequate for therapy of P. carinii pneumonia, but infants between 3 and 24 months of age may requ ire a dosage of 35 mg/kg/day.