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JAC Advance Access published online on April 20, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl141
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received December 8, 2005
Revised March 17, 2006
Accepted March 22, 2006

Original article

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

Helene Vogelsinger 1, Stefan Weiler 1, Angela Djanani 2, Jordan Kountchev 3, Rosa Bellmann-Weiler 4, Christian J. Wiedermann 5, and Romuald Bellmann 6 *

1 Clinical Pharmacokinetics Unit, Laboratory of Inflammation Research, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria
2 Inflammation Research Unit, Laboratory of Inflammation Research, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria
3 Intensive Care Unit, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria
4 Infectious Diseases Unit, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria
5 Clinical Pharmacokinetics Unit, Laboratory of Inflammation Research, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria; Inflammation Research Unit, Laboratory of Inflammation Research, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria; Present address. Department of Internal Medicine, General Hospital of Bolzano, Bolzano, Italy
6 Clinical Pharmacokinetics Unit, Laboratory of Inflammation Research, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria; Intensive Care Unit, Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria

* To whom correspondence should be addressed.
Romuald Bellmann, E-mail: romuald.bellmann{at}uibk.ac.at


  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.

Keywords: antimycotics; lipid-formulated amphotericin B; tissue penetration; lung concentration; invasive fungal infections.
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