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Liposomal amphotericin B-the past
R J Brüggemann1,2, G M Jensen3, C Lass-Flörl4
1Department of Pharmacy, and Radboudumc Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Abstract:
The discovery of amphotericin B, a polyene antifungal compound, in the 1950s, and the formulation of this compound in a liposomal drug delivery system, has resulted in decades of use in systemic fungal infections. The use of liposomal amphotericin B formulation is referenced in many international guidelines for the treatment of fungal infections such as Aspergillus and cryptococcal disease and Candida infections, as well as other less common infections such as visceral leishmaniasis. With the development of liposomal amphotericin B, an improved therapeutic index could be achieved that allowed the attainment of higher drug concentrations in both the plasma and tissue while simultaneously lowering the toxicity compared with amphotericin B deoxycholate. In over 30 years of experience with this drug, a vast amount of information has been collected on preclinical and clinical efficacy against a wide variety of pathogens, as well as evidence on its toxicity. This article explores the history and nature of the liposomal formulation, the key clinical studies that developed the pharmacokinetic, safety and efficacy profile of the liposomal formulation, and the available microbiological data.
Insights
Liposomal amphotericin B, a key antifungal treatment, offers improved efficacy and safety for systemic fungal infections. Decades of research confirm its value in treating serious infections like aspergillosis and candidiasis.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Amphotericin B, a polyene antifungal, has been vital for treating systemic fungal infections since the 1950s.
- Liposomal amphotericin B formulation enhances drug delivery, improving therapeutic index by increasing plasma and tissue concentrations while reducing toxicity compared to conventional amphotericin B deoxycholate.
Purpose of the Study:
- To review the history and characteristics of liposomal amphotericin B.
- To examine key clinical studies detailing its pharmacokinetic, safety, and efficacy profile.
- To present available microbiological data on its effectiveness against various pathogens.
Main Methods:
- Literature review of historical data, preclinical studies, and clinical trials.
- Analysis of pharmacokinetic and safety data from clinical use.
- Compilation of microbiological efficacy data against fungal and protozoan pathogens.
Main Results:
- Liposomal amphotericin B is established in international guidelines for treating infections like aspergillosis, cryptococcosis, candidiasis, and visceral leishmaniasis.
- Over 30 years of use provide extensive data on its preclinical and clinical efficacy and toxicity.
- The liposomal formulation demonstrates a favorable safety and efficacy profile for a broad spectrum of pathogens.
Conclusions:
- Liposomal amphotericin B represents a significant advancement in managing systemic fungal infections.
- Its established safety and efficacy profile supports its continued use and recommendation in clinical practice.
- Ongoing research and data collection continue to refine understanding of its therapeutic applications.
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