2. Academic Validation
  3. Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B

Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B

  • Clin Infect Dis. 2019 May 2;68(Suppl 4):S244-S259. doi: 10.1093/cid/ciz064.
Jill Adler-Moore 1,  Russell E Lewis 2,  Roger J M Brüggemann 3,  Bart J A Rijnders 4,  Andreas H Groll 5,  Thomas J Walsh 6
Affiliations

Affiliations

  • 1 Department of Biological Sciences, California State Polytechnic University, Pomona.
  • 2 Unit of Infectious Diseases, Policlinico Sant'Orsola-Malpighi, Department of Medical Sciences and Surgery, University of Bologna, Italy.
  • 3 Department of Pharmacy, Radboud University Medical Centre, Nijmegen, The Netherlands.
  • 4 Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
  • 5 Infectious Disease Research Program, Department of Pediatric Hematology and Oncology and Center for Bone Marrow Transplantation, University Children's Hospital Muenster, Germany.
  • 6 Departments of Medicine, Pediatrics, and Microbiology & Immunology, Weill Cornell Medicine of Cornell University, New York, New York.
PMID: 31222254 DOI: 10.1093/cid/ciz064
Abstract

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.

Keywords

LAmB; liposomal amphotericin B; pharmacodynamics; pharmacokinetics; preclinical.

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