Amphotericin B tissue distribution in autopsy material after treatment with liposomal amphotericin B and amphotericin B colloidal dispersion

J Antimicrob Chemother. 2006 Jun;57(6):1153-60. doi: 10.1093/jac/dkl141. Epub 2006 Apr 20.

Abstract

Objectives: Tissue concentrations of amphotericin B were determined in autopsy material of patients who had been treated with liposomal amphotericin B or amphotericin B colloidal dispersion (colloidal amphotericin B) for suspected or proven invasive fungal infection.

Patients and methods: Amphotericin B tissue levels were measured in liver, spleen, lung, kidney, and myocardial and brain tissue of 20 patients who had been treated with lipid-formulated amphotericin B, before they died from multi-organ failure. Seven patients had been treated with liposomal amphotericin B (AmBisome) and thirteen with colloidal amphotericin B (Amphocil). Tissue samples were obtained during routine autopsy, homogenized and extracted with methanol. Amphotericin B concentrations were measured using HPLC after purification by solid phase extraction.

Results: The highest amphotericin B levels were found in liver and spleen, followed by kidney, lung, myocardium and brain. In the lung higher amphotericin B concentrations were found after treatment with amphotericin B colloidal dispersion than after therapy with liposomal amphotericin B.

Conclusions: The choice of lipid formulation may influence amphotericin B penetration into the lung.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amphotericin B / analysis*
  • Amphotericin B / pharmacokinetics
  • Autopsy
  • Brain Chemistry
  • Chromatography, High Pressure Liquid
  • Female
  • Humans
  • Kidney / chemistry
  • Liver / chemistry
  • Lung / chemistry
  • Male
  • Middle Aged
  • Multiple Organ Failure
  • Mycoses / complications
  • Mycoses / drug therapy
  • Myocardium / chemistry
  • Spleen / chemistry
  • Tissue Distribution
  • Tissue Extracts / chemistry
  • Tissue Extracts / isolation & purification

Substances

  • Tissue Extracts
  • liposomal amphotericin B
  • Amphotericin B