ABSTRACT
Amphotericin B (AmB) was the first available systemic antifungal drug. The deoxycholate formation has been in use since the mid-1950s and remained the primary systemic antifungal until the development of the triazoles in the late 1980s. AmB was the first-line treatment for most life-threatening systemic antifungal infections both because it was the only choice and also because of its potency and broad spectrum of activity. The predominant factor, which has made use of this compound difficult, is the associated dose-limiting nephrotoxicity. More recent development of less-toxic lipid formulations of AmB has significantly improved the therapeutic drug window for this drug class (1). The fungal disease for which AmB remains the best first-line option is cryptococcal meningitis (2). However, the drug continues to be recommended in most treatment guidelines as a first-line alternative for invasive Candida, Aspergillus, and severe endemic fungal infections (3-5). Pharmacokinetics and pharmacodynamics have not traditionally been considered in the development of antifungal dosing regimens. Recent in vitro and in vivo investigations have examined the pharmacodynamic characteristics of the polyene antifungals. Results from these studies should be useful for design of rationale dosing strategies to both optimize efficacy and limit toxicity.
