Determination of the Relative Toxicity of Amphotericin B Formulations: A Red Blood Cell Potassium Release Assay

Amphotericin B remains the drug of choice for the treatment of life-threatening, systemic fungal infections. Nevertheless, the use of amphotericin B in the traditional deoxycholate formulation (d-AmB) is limited by severe toxic side effects. Several relatively new formulations have recently received regulatory approval: amphotericin B colloidal dispersion (ABCD), amphotericin B lipid complex (ABLC), and liposomal amphotericin B (AmBisome). We quantitate the level of reduction of intrinsic toxicity of these formulations over d-AmB using a red blood cell potassium release assay, employing a variety of blood sources and incubation times. We also examine the practice of diluting d-AmB in the parenteral nutrition product Intralipid. Overall, the propensity in each formulation of amphotericin B to partition into the red cell membrane during incubation is measured by determining the concentration of amphotericin B required to achieve 50% potassium release. The concentrations leading to 50% potassium release were...

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