Therapeutic drug monitoring of liposomal amphotericin B in children. Are we there yet? A systematic review

Introduction: Therapeutic drug monitoring (TDM) is a tool that supports personalized dosing, but its role for liposomal amphotericin B (L-amb) is unclear. This systematic review assessed the evidence for L-amb TDM in children.

Objectives: To evaluate the concentration–efficacy relationship, concentration–toxicity relationship and pharmacokinetic/pharmacodynamic (PK/PD) variability of L-amb in children.

Methods: We systematically reviewed PubMed and Embase databases following PRISMA guidelines. Eligible studies included L-amb PK/PD studies in children aged 0–18 years. Review articles, case series of <five patients, editorials and animal studies were excluded. Quality assessment was performed using the Critical Appraisal of Clinical Pharmacokinetics tool. The concentration–efficacy and concentration–toxicity relationships and PK/PD variability were analysed.

Results: In total, 4220 studies were screened; 6 were included, presenting data on 195 children. Invasive candidiasis and aspergillosis were the two most common infections treated with L-amb. Studies showed significant PK variability due to age (mean age ranged from 14 days to 17 years), body weight, non-linear PK and changes in the volume of distribution. Limited evidence supported a peak concentration/MIC (C_max/MIC) of 25–50 for optimal efficacy and an AUC₂₄ of >600 mg·h/L for nephrotoxicity. L-amb doses of 2.5–10 mg/kg/day were reported to achieve C_max/MIC > 25 using an MIC of 1 mg/L.

Conclusions: While significant PK variability was observed in children, evidence to support routine L-amb TDM was limited. Further studies on efficacy and toxicity benefits are required before routine TDM of L-amb can be recommended.