Document Type

Journal Article

Publication Date

12-1-2016

Journal

Antimicrobial Agents and Chemotherapy

Volume

60

Issue

12

DOI

10.1128/AAC.01427-16

Keywords

Adolescent; Amphotericin B; Antifungal Agents; Area Under Curve; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Humans; Immunocompromised Host; Infant; Invasive Fungal Infections; Male

Abstract

Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg(-1) daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (n = 35 patients) and on the final day of therapy (n = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (n = 13) having significantly higher maximum serum concentrations (Cmax) and areas under the concentration-time curve from 0 to 24 h (AUC0-24) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of

Creative Commons License

Creative Commons License
This work is free of known copyright restrictions.

Peer Reviewed

1

Open Access

1

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