Treatment of Experimental Invasive Pulmonary Aspergillosis in Rats with Liposomal Amphotericin B.
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概要
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Liposomal amphotericin B was evaluated for toxicity, pharmacokinetic properties and therapeutic efficacy in invasive pulmonary aspergillosis in Sprague-Dawley rats. The protective effect of liposomes against the toxicity induced by repeated amphotericin B infusions was observed in a survival study of rats, thereby allowing higher dosages to be administered. Pharmacokinetic studies showed that liposomes led to high levels of amphotericin B in the spleen and liver. Drug levels in the lung were higher at ten minutes after intravenous injection of liposomal amphotericin B at 20mg/kg than of free amphotericin B at 1.5mg/kg. Efficacy was assessed in rats treated with cortisone acetate, fed a low-protein diet and infected transtracheally with 8×10<SUP>4</SUP> <I>Aspeygillus fumigatus</I> spores to cause fetal pneumonia and pulmonary bleeding. Dosages of 20 or 4mg/kg of liposomal amphotericin B, or 1.5mg/kg of free amphotericin B were administered intravenously to rats once daily for 8 days. Control rats received saline. Twenty mg/kg of liposomal amphotericin B was as effective on survival rate as 1.5mg/kg of free amphotericin B. However, 4mg/kg of liposomal amphotericin B was less effective than 1.5mg/kg of free amphotericin B, prolonging the mean survival time of rats treated with saline, which showed elevation of galactomannan antigen titers of <I>Aspeygillus fumigatus</I> in sera and invasive proliferation or mycelia with bleeding in histopathological sections of the lung. We conclude that liposomal amphotericin B reduces toxicity of the drug, thereby increasing the concentration of the drug in the lung by high-dose administration, but decreases the efficacy of the drug in experimental pulmonary aspergillosis.
- The Japanese Association for Infectious Diseasesの論文
The Japanese Association for Infectious Diseases | 論文
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