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


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.
Vogelsinger
Helene
H
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.
Weiler
Stefan
S
Djanani
Angela
A
Kountchev
Jordan
J
Bellmann-Weiler
Rosa
R
Wiedermann
Christian J
CJ
Bellmann
Romuald
R
D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000032:analysis* / Q000493:pharmacokinetics; D001344:Autopsy; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007668:Kidney / Q000737:chemistry; D008099:Liver / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure; D009181:Mycoses / Q000150:complications / Q000188:drug therapy; D009206:Myocardium / Q000737:chemistry; D013154:Spleen / Q000737:chemistry; D014018:Tissue Distribution; D014020:Tissue Extracts / Q000737:chemistry / Q000302:isolation & purification
D014020:Tissue Extracts; C068538:liposomal amphotericin B; D000666:Amphotericin B