Abstract
In this study, rational dosing guidelines for amphotericin B-deoxycholate (AmB) are proposed for children. AmB steady-state trough concentrations (Css,trough) and plasma creatinine concentrations (Ccreat) were measured in 83 children (age: 10 months to 18 years) receiving prophylactic AmB therapy (1 mg/kg/day). Maximum tolerable AmB Css,trough were identified by determining the probability of large (>24%, 75th percentile) increases in Ccreat after 6 days of AmB for a series of Css,trough ranges. Dose requirements were determined using a concentration-targeting approach. The 0.76–1.05 mg/l Css,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 Css,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 Css,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.