Amphotericin B is the most effective agent for the majority of systemic
fungal infections but often causes toxicity, and specific dosage guidelines for
amphotericin B in pediatric patients are lacking. The purpose of this study was to characterize the pharmacokinetics of
amphotericin B in children. Twelve patients (mean age, 6.6 years; range, 4 months to 14 years) receiving
amphotericin B, 0.68 +/- 0.34 mg/kg per day (mean plus or minus standard deviation), were studied. Four to eight blood samples were collected during a 24-h period and analyzed by high-pressure liquid chromatography. The peak concentration of
amphotericin B in serum was 2.9 +/- 2.8 micrograms/ml. The mean total clearance, apparent volume of distribution, and elimination half-life were 0.46 +/- 0.20 ml/min per kg, 0.76 +/- 0.52 liters/kg, and 18.1 +/- 6.6 h, respectively. Total clearance decreased with age (p less than 0.01). In children aged 8 months to 9 years, the mean total clearance was 0.57 +/- 0.15 ml/min per kg, and in children older than 9 years, it was 0.24 +/- 0.02 ml/min per kg. Interpatient variation in the clearance and volume of distribution of
amphotericin B was greater than threefold and greater than eightfold, respectively. However, pharmacokinetic parameters did not change in two stable patients who were studied again. Because clearance decreased substantially with age, older children may require lower doses of
amphotericin B per kilogram to decrease the potential for toxicity.