Distribution and Activity of Amphotericin B in Humans

Concentrations of amphotericin B (AmB) in tissues obtained at autopsy from eight patients were measured by high-performance liquid chromatography (HPLC). The patients had received doses of 101–2,688 mg of antibiotic. Highest concentrations of the drug were found in the liver; in one patient the amou...

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Bibliographic Details
Published in:The Journal of infectious diseases 1985-11, Vol.152 (5), p.1037-1043
Main Authors: Christiansen, Keryn J., Bernard, Edward M., Gold, Jonathan W. M., Armstrong, Donald
Format: Article
Language:English
Subjects:
Amphotericin B - analysis
Amphotericin B - metabolism
Amphotericin B - pharmacology
Amphotericin B - therapeutic use
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antifungal agents
Antifungals
Aspergillosis - drug therapy
Aspergillosis - metabolism
Aspergillosis - microbiology
Aspergillus - drug effects
Aspergillus - isolation & purification
Autopsies
Bioassay
Biological and medical sciences
Biological Assay
Candida - drug effects
Candida - isolation & purification
Candidiasis - drug therapy
Candidiasis - metabolism
Candidiasis - microbiology
Chromatography, High Pressure Liquid
Dosage
Ethanol
Humans
Kidney - analysis
Kidneys
Liver
Liver - analysis
Lung - analysis
Medical sciences
Metabolism
Myocardium - analysis
Original Articles
Pharmacology. Drug treatments
Spleen
Spleen - analysis
Tissue Distribution
Urine
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Summary:Concentrations of amphotericin B (AmB) in tissues obtained at autopsy from eight patients were measured by high-performance liquid chromatography (HPLC). The patients had received doses of 101–2,688 mg of antibiotic. Highest concentrations of the drug were found in the liver; in one patient the amount of AmB in the liver was 41% of the total dose. No evidence of metabolism of the drug was observed, and bioassay of ethanol extracts of tissue showed that the drug retained activity. Three of the patients had histologic evidence of aspergillar or candidal infection in tissues with concentrations of AmB ranging from 2.5 to 166 µg/g. With two patients, the concentrations of the drug in the tissues exceeded by ⩾10-fold the minimum inhibitory concentrations of the drug in isolates that had been obtained from the same tissues. Unknown factors present in tissues appear to limit the in vivo activity of AmB.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/152.5.1037