Pharmacokinetics of Amphotericin B in Infants and Children

Abstract

The pharmacokinetics of amphotericin B (AmB) have not previously been evaluated in children. Five very small, premature infants and five older children received 0.25–1.0 mg of AmB/kg per 24 hr for Candida infections. Serum concentrations of AmB, measured by bioassay, were used to determine various pharmacokinetic parameters of AmB. A onecompartment model of drug distribution was most consistent with the data. The volume of AmB distributed per kilogram of body weight was smaller and the elimination clearance more rapid than those previously reported for adults. Serum levels were approximately one-half those seen in adults given comparable doses. The mean concentrations of AmB after various doses were as follows: at 0.25 mg/kg, 0.08 μg/ml; at 0.50 mg/kg, 0.20 μg/ml; at 0.75 mg/kg, 0.42 μg/ml; and at 1.0 mg/kg, 0.54 μg/ml. Interpatient variability was, however, marked, especially among the premature infants. AmB pharmacokinetics are different in infants and children than in adults; these differences may have implications for determining optimal pediatric dosing regimens.