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  • Title: Pharmacological parameters of intravenously administered amphotericin B in rats: comparison of the conventional formulation with amphotericin B associated with a triglyceride-rich emulsion.
    Author: Souza LC, Campa A.
    Journal: J Antimicrob Chemother; 1999 Jul; 44(1):77-84. PubMed ID: 10459813.
    Abstract:
    The LD50 determined in rats for the potent antifungal amphotericin B (AB) increased from 4.2 to 12.0 when the conventional AB-deoxycholate (DOC) was compared with AB associated with a triglyceride-rich emulsion (AB-emulsion). The reduction in amphotericin B toxicity is not due to a modification in plasma clearance, as both formulations seem to be removed from plasma at the same rate. Major differences in amphotericin B tissue distribution were not seen for kidney and liver but were seen for the lung. After 24 h administration of a single amphotericin B dose (2.0 mg/kg body weight) 23.78 +/- 11.71 mg/kg tissue was recovered from the lung of animals treated with AB-DOC whereas for AB-emulsion only 5.19 +/- 2.50 mg/kg tissue was recovered. The higher lethality of AB-DOC may be related to the higher concentration of amphotericin B in the lung. The therapeutic efficacy of AB-emulsion was similar to that of AB-DOC as attested by survival curves obtained after treatment of mice infected by Candida albicans. This is highly relevant, as the same is not necessarily found for other less toxic proposed vehicles. The equivalent efficacy and the increment in the LD50 will result in an important improvement in the therapeutic activity of amphotericin B. Furthermore, some data related to storage and stability indicate the clinical utility of this type of drug delivery.
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