Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B
Publication year
2019Source
Clinical Infectious Diseases, 68, Supplement_4, (2019), pp. S244-S259ISSN
Publication type
Article / Letter to editor

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Organization
Clinical Pharmacy
Journal title
Clinical Infectious Diseases
Volume
vol. 68
Issue
iss. Supplement_4
Page start
p. S244
Page end
p. S259
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIHS: Radboud Institute for Health SciencesAbstract
The improved safety profile and antifungal efficacy of liposomal amphotericin B (LAmB) compared to conventional amphotericin B deoxycholate (DAmB) is due to several factors including, its chemical composition, rigorous manufacturing standards, and ability to target and transit through the fungal cell wall. Numerous preclinical studies have shown that LAmB administered intravenously distributes to tissues frequently infected by fungi at levels above the minimum inhibitory concentration (MIC) for many fungi. These concentrations can be maintained from one day to a few weeks, depending upon the tissue. Tissue accumulation is dose-dependent with drug clearance occurring most rapidly from the brain and slowest from the liver and spleen. LAmB localizes in lung epithelial lining fluid, within liver and splenic macrophages and in kidney distal tubules. LAmB has been used successfully in therapeutic and prophylactic animal models to treat many different fungal pathogens, significantly increasing survival and reducing tissue fungal burden.
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