Liposomal Amphotericin B (AmBisome®): A Review of the Pharmacokinetics, Pharmacodynamics, Clinical Experience and Future Directions

Abstract

Liposomal amphotericin B (AmBisome®; LAmB) is a unique lipid formulation of amphotericin B. LAmB is a standard of care for a wide range of medically important opportunistic fungal pathogens. LAmB has a significantly improved toxicity profile compared with conventional amphotericin B deoxycholate (DAmB). Despite nearly 20 years of clinical use, the pharmacokinetics and pharmacodynamics of this agent, which differ considerably from DAmB, remain relatively poorly understood and underutilized in the clinical setting.The molecular pharmacology, preclinical and clinical pharmacokinetics, and clinical experience with LAmB for the most commonly encountered fungal pathogens are reviewed. In vitro, experimental animal models and human clinical trial data are summarized, and novel routes of administration and dosing schedules are discussed.LAmB is a formulation that results in reduced toxicity as compared with DAmB while retaining the antifungal effect of the active agent. Its long terminal half-life and retention in tissues suggest that single or intermittent dosing regimens are feasible, and these should be actively investigated in both preclinical models and in clinical trials. Significant gaps remain in knowledge of pharmacokinetics and pharmacodynamics in special populations such as neonates and children, pregnant women and obese patients.

Retrospective Cohort Analysis of Liposomal Amphotericin B Nephrotoxicity in Patients with Hematological Malignancies

“…Recent clinical studies have suggested limited benefits and higher risk of nephrotoxicity with increasing daily doses of L-AMB in the treatment of cryptococcal meningitis (17), invasive aspergillosis (18), and possibly mucormycosis (19). However, novel dosing approaches using a combination of high induction doses followed by lower maintenance doses are under investigation for cryptococcosis (20,21).…”

Biodistribution and In Vivo Antileishmanial Activity of 1,2-Distigmasterylhemisuccinoyl- sn -Glycero-3-Phosphocholine Liposome-Intercalated Amphotericin B

“…Since Fungizone, the micellar formulation of AMB, quickly releases its payload following administration, it causes severe toxic adverse effects, including acute infusion-related toxicities and chronic nephrotoxicity, which limit its clinical use (14). Three different lipid-based nanoformulations of AMB (Amphotec, Abelcet, and AmBisome) have been developed and commercialized in the United States and Europe in order to increase tolerance and the therapeutic index of AMB and to reduce drugrelated adverse effects (15). Liposomal AMB is widely used in the treatment of VL (11).…”

The care and feeding of a commercial liposomal product: liposomal amphotericin B (AmBisome®)

“…in catheters; and continued understanding of pharmacokinetics/pharmacodynamics, of pediatric usage, and of mechanism of action. See Stone et al (2016).…”