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  • Title: Efficacy of alternative dosing regimens of poly-aggregated amphotericin B.
    Author: Espada R, Valdespina S, Molero G, Dea MA, Ballesteros MP, Torrado JJ.
    Journal: Int J Antimicrob Agents; 2008 Jul; 32(1):55-61. PubMed ID: 18534826.
    Abstract:
    A new poly-aggregated form of amphotericin B was formulated as a non-microencapsulated form (P-AMB) or incorporated in albumin microspheres (MP-AMB) and compared with the conventional amphotericin B formulation (D-AMB). Mice were infected with Candida albicans and treated with two different intermittent dose regimens of the different amphotericin B formulations. Efficacy and toxicity were studied by the determination of survival rate, kidney colony-forming units counts, biochemical parameters and amphotericin B concentrations in plasma and organs. All the treatments significantly (P<0.05) increased the survival rate in relation to the untreated group, although non-statistically significant differences (P>0.05) were found between formulations and dosing regimens. All the treatments produced kidney toxicity, expressed by high urea levels. Kidney toxicity was especially significant for mice treated with the D-AMB formulation where unilateral kidney atrophy was observed in most of the mice, whereas most of the mice treated with P-AMB conserved both kidneys with a normal size and appearance. At 45 days post infection, variable distribution of amphotericin B in the body was obtained depending on the amphotericin B formulation. In conclusion, non-daily dosing regimens of P-AMB, which is less toxic than D-AMB, could be used as an alternative to the conventional D-AMB formulation to treat experimental candidiasis.
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