Amphotericin B dose optimization in children with malignant diseases.

ABSTRACT

In this study, rational dosing guidelines for amphotericin B-deoxycholate (AmB) are proposed for children. AmB steady-state trough concentrations (C(ss,trough)) and plasma creatinine concentrations (C(creat)) were measured in 83 children (age 10 months to 18 years) receiving prophylactic AmB therapy (1 mg/kg/day). Maximum tolerable AmB C(ss,trough) were identified by determining the probability of large (>24%, 75th percentile) increases in C(creat) after 6 days of AmB for a series of C(ss,trough) ranges. Dose requirements were determined using a concentration-targeting approach. The 0.76-1.05 mg/l C(ss,trough) range provided the maximum concentrations that still had a low probability (p < 0.29) of adverse renal effects. 1 mg/kg/day AmB produces C(ss,trough) within this range for children weighing 25-45 kg. Lighter children (10-25 kg) require higher AmB doses (1.25-1.5 mg/kg/day) to achieve target C(ss,trough), while heavier children (45-55 kg) require lower doses (0.75 mg/kg/day). These starting dose guidelines may require individualization and prospective evaluation.