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Related Experiment Videos

High purity amphotericin B.

John D Cleary1, Stanley W Chapman, Edwin Swiatlo

  • 1Schools of Pharmacy and Medicine, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4500, USA. jcleary@medicine.umsmed.edu

The Journal of Antimicrobial Chemotherapy
|October 9, 2007
PubMed
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High purity Amphotericin B (AmBHP) shows equal or better efficacy than generic Amphotericin B (AmB) in treating fungal infections, with significantly reduced toxicity in both cell cultures and animal models.

Area of Science:

  • Mycology
  • Pharmacology
  • Medicinal Chemistry

Background:

  • Amphotericin B (AmB) is a primary treatment for disseminated fungal infections.
  • Current AmB formulations are associated with severe adverse effects.
  • Generic AmB contains multiple polyene components, suggesting potential for improved formulations.

Purpose of the Study:

  • To develop and evaluate a high purity Amphotericin B (AmBHP) formulation.
  • To compare the therapeutic index of AmBHP against existing AmB formulations.
  • To assess the efficacy and toxicity of AmBHP in vitro and in vivo.

Main Methods:

  • Isolation of AmBHP from generic AmB using semi-preparative reverse-phase high-pressure liquid chromatography.
  • In vitro efficacy testing against Candida albicans.

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  • In vivo efficacy and toxicity studies in a Candida-infected mouse model, including assessment of LD(50) and glomerular filtration rate.

    • Main Results:

    • AmBHP demonstrated comparable in vitro activity to generic AmB.
    • AmBHP exhibited similar efficacy to generic and lipid-complexed AmB in a murine fungal infection model.
    • AmBHP showed reduced toxicity to human monocytic cells at low concentrations and lower general in vivo toxicity compared to generic and lipid-complexed AmB.
    • AmBHP caused approximately half the reduction in glomerular filtration rate compared to a significantly lower dose of generic AmB.

    Conclusions:

    • High purity Amphotericin B (AmBHP) formulation offers a potential improvement over current AmB products.
    • AmBHP provides equivalent or enhanced antifungal efficacy with a reduced toxicity profile.
    • These findings suggest AmBHP could represent a safer and more effective therapeutic option for disseminated fungal infections.