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JAC Advance Access originally published online on April 20, 2006
Journal of Antimicrobial Chemotherapy 2006 57(6):1153-1160; 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

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

Helene Vogelsinger1, Stefan Weiler1, Angela Djanani2, Jordan Kountchev3, Rosa Bellmann-Weiler4, Christian J. Wiedermann1,2,{dagger} and Romuald Bellmann1,3,*

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

Received 8 December 2005; returned 5 February 2006; revised 17 March 2006; accepted 22 March 2006

*Correspondence address. Division of General Internal Medicine, Department of Internal Medicine, Innsbruck Medical School, Anichstrasse 35, A-6020 Innsbruck, Austria. Tel: +43-512-504-81389; Fax: + 43-512-504-24199; E-mail: romuald.bellmann{at}uibk.ac.at

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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