Efficacy of alternative dosing regimens of poly-aggregated amphotericin B

Raquel Espada1, Suriñe Valdespina, Gloria Molero

  • 1Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Plaza Ramón y Cajal s/n, Madrid, Spain.

Insights

A novel poly-aggregated amphotericin B formulation (P-AMB) shows comparable efficacy to conventional amphotericin B (D-AMB) in treating candidiasis but with significantly reduced kidney toxicity, offering a less toxic alternative.

Area of Science:

  • Mycology
  • Pharmacology
  • Toxicology

Background:

  • Amphotericin B is a critical antifungal agent for treating invasive candidiasis.
  • Conventional amphotericin B formulations (D-AMB) are associated with significant nephrotoxicity.
  • Novel drug delivery systems aim to improve amphotericin B efficacy and reduce toxicity.

Purpose of the Study:

  • To evaluate the efficacy and toxicity of a new poly-aggregated amphotericin B formulation (P-AMB) and its microencapsulated variant (MP-AMB) compared to D-AMB.
  • To assess the impact of intermittent dosing regimens on treatment outcomes.
  • To investigate the pharmacokinetic profile and organ distribution of different amphotericin B formulations.

Main Methods:

  • Formulation of P-AMB and MP-AMB, with D-AMB as a control.
  • Experimental model of candidiasis in mice infected with Candida albicans.
  • Intermittent dosing regimens were administered to assess survival rates, kidney toxicity (urea levels, colony counts, organ morphology), and drug concentrations in plasma and organs.

Main Results:

  • All amphotericin B formulations significantly improved survival rates compared to untreated controls.
  • No statistically significant differences in efficacy were observed between the different formulations and dosing regimens.
  • P-AMB treatment resulted in significantly less kidney toxicity and preservation of kidney morphology compared to D-AMB.

Conclusions:

  • Non-daily dosing regimens of P-AMB demonstrate reduced toxicity compared to D-AMB.
  • P-AMB presents a promising, less toxic alternative to conventional amphotericin B for treating experimental candidiasis.
  • Further research into P-AMB's pharmacokinetic and toxicological profile is warranted.

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