Lipid Formulations for Amphotericin B: Does the Emperor Need New Clothes?

Although the three defined preparations clearly reduce nephrotoxicity, they are not licensed in the United States, and use of these drugs has been significantly limited by their costs, which may reach $500 to $1000 per day for doses of 5 mg/kg.

Abstract

Editorials15 May 1996Lipid Formulations for Amphotericin B: Does the Emperor Need New Clothes?John R. Graybill, MDJohn R. Graybill, MDUniversity of Texas Health Science Center at San Antonio, San Antonio, TX 78284Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-124-10-199605150-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail For many years, the polyene amphotericin B deoxycholate (AMBd) has been the emperor of systemic antifungal therapy. Unfortunately, the great efficacy of amphotericin B has been matched by substantial toxicity. Efforts to develop less toxic alternatives to AMBd have focused on repackaging amphotericin B in new clothes, that is, lipid vehicles. These vehicles have been designed to target sites of fungal infection but spare the kidneys [1-5]. In general, lipid-associated amphotericin B preparations achieve lower renal concentrations than does AMBd, and they are concentrated in reticuloendothelial tissues such as the liver and spleen. Pharmacokinetics variables, including tissue distribution and clearance, ...References1. Schmitt HJ. New methods of delivery of amphotericin B. Clin Infect Dis. 1993; 17(Suppl 2):S501-6. Google Scholar2. de Marie S, Janknegt R, Bakker-Woudenberg IA. Clinical use of liposomal and lipid-complexed amphotericin B. J Antimicrob Chemother. 1994; 33:907-16. Google Scholar3. Sanders SW, Buchi KN, Goddard MS, Lang JK, Tolman KG. Single-dose pharmacokinetics and tolerance of a cholesteryl sulfate complex of amphotericin B administered to healthy volunteers. Antimicrob Agents Chemother. 1991; 35:1029-34. Google Scholar4. Janknegt R, de Marie S, Bakker-Woudenberg IA, Crommelin DJA. Liposomal and lipid formulations of amphotericin B. Clinical pharmacokinetics. Clin Pharmacokinet. 1992; 23:279-91. 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Liposomal amphotericin B prevents invasive fungal infections in liver transplant recipients. A randomized, placebo-controlled study. Transplantation. 1995; 59:45-50. Google Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Health Science Center at San Antonio, San Antonio, TX 78284Corresponding Author: John R. Graybill, MD, Division of Infectious Diseases, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284. 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Part I. Amphotericin B Preparations and FlucytosineFebrile Neutropenie: Praktische AspekteAntifungals: mechanism of action and resistance, established and novel drugsPolymeric micelles for drug delivery: solubilization and haemolytic activity of amphotericin BLiposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitisAntibiotic treatment of systemic fungal infectionsAntifungal treatment in patients with cancerAmphotéricine B déoxycholate (Fungizone®): vieux médicament, nouvelles versions 15 May 1996Volume 124, Issue 10Page: 921-923KeywordsAmphotericinAspergillosisCandidiasisCerebrospinal fluidCoccidioidomycosisCryptococcosisDrugsLipidsMycosesToxicity Issue Published: 15 May 1996 CopyrightCopyright © 1996 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...