Toxicokinetic and mechanistic basis for the safety and tolerability of liposomal amphotericin B.
BACKGROUND
Amphotericin B (AmB) was first approved by the US Food and Drug Administration in 1959 with sodium deoxycholate (DAmB, Fungizone®). Extensive toxicities associated with the drug led to the development of lipid formulations of AmB, including liposomal amphotericin B (L-AmB, AmBisome®). Phase I studies as well as comparative Phase III clinical trials indicate that L-AmB is associated with less nephrotoxicity and reduced infusion-related toxicity. There is, however, no recent comprehensive review of the safety and tolerability of L-AmB.


METHODS
This article reviews the safety, tolerability and the mechanisms of the major toxicities associated with L-AmB, including nephrotoxicity, infusion-related reactions (IRRs), anemia and thrombocytopenia, and hepatic abnormalities. The article further discusses the mechanism of action and pharmacokinetics of L-AmB.


CONCLUSIONS
L-AmB is a broad-spectrum antifungal agent that has significantly reduced toxicities compared to its predecessor, DAmB.
NewYork-Presbyterian/Weill Cornell Medical Center, Department of Pharmacy , 525 East 68th St, NY 10065 , USA.
Angela S
AS
Loo
Saif A
SA
Muhsin
Thomas J
TJ
Walsh
D000666:Amphotericin B / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000494:pharmacology; D002986:Clinical Trials as Topic; D017277:Drug Approval; D006801:Humans; D009181:Mycoses / Q000188:drug therapy; D014481:United States; D014486:United States Food and Drug Administration
D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B