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Amphotericin B transfer to CSF following intravenous administration of liposomal amphotericin B

Volker Strenger1, Andreas Meinitzer2, Josef Donnerer3

  • 1Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria volker.strenger@medunigraz.at.

The Journal of Antimicrobial Chemotherapy
|June 4, 2014
PubMed
Abstract

Insights

Liposomal amphotericin B (LAmB) administered intravenously results in low but sustained cerebrospinal fluid (CSF) levels of amphotericin B (AmB) in pediatric patients. These levels remain steady for over 48 hours, potentially allowing for effective treatment of CNS fungal infections.

Area of Science:

  • Pharmacokinetics
  • Neuroscience
  • Infectious Diseases

Background:

  • Amphotericin B (AmB) and its lipid formulations are crucial for treating central nervous system (CNS) fungal infections.
  • The cerebrospinal fluid (CSF) pharmacokinetics of liposomal amphotericin B (LAmB) after intravenous administration are not well understood.

Purpose of the Study:

  • To characterize the CSF kinetics of AmB following intravenous LAmB administration in pediatric patients.
  • To determine AmB concentrations in CSF and serum and calculate transfer rates.

Main Methods:

  • CSF and serum samples were collected from 14 pediatric patients receiving prophylactic intravenous LAmB (3 mg/kg/day).
  • Samples were analyzed for AmB using High-Performance Liquid Chromatography (HPLC).
  • 30 CSF samples were obtained at various time points post-infusion.

Main Results:

  • CSF AmB levels ranged from 10-120 ng/mL, with one outlier at 529 ng/mL, 1-100 hours post-infusion.
  • Serum levels were approximately 1000-fold higher than CSF levels.
  • CSF levels exhibited a steady-state for over 48 hours, with a transfer rate of 0.02%-0.92% from serum.

Conclusions:

  • Intravenous LAmB yields low but sustained AmB concentrations in CSF.
  • The steady-state CSF levels persist beyond 48 hours.
  • Higher brain tissue concentrations may be achievable, suggesting potential efficacy for CNS fungal infections.
Keywords:
AmBisomeHPLCblood–brain barrierliposomal amphotericin Btransfer rate

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