JAC Advance Access originally published online on January 30, 2006
Journal of Antimicrobial Chemotherapy 2006 57(4):724-731; doi:10.1093/jac/dkl005
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Comparative study on the efficacy of AmBisome and Fungizone in a mouse model of pulmonary aspergillosis
1 Discovery Research Laboratories II, Sumitomo Pharmaceuticals Research Division, 1-98, Kasugadenaka 3-chome, Konohana-ku, Osaka 554-0022, Japan; 2 Division of Respiratory Disease, Department of Medicine, Kawasaki Medical School, 577, Matsushima, Kurashiki 701-0192, Japan
Received 28 July 2005; returned 25 September 2005; revised 8 November 2005; accepted 23 December 2005
* Corresponding author. Present address: Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co., Ltd., 1-98, Kasugadenaka 3-chome, Konohana-ku, Osaka 554-0022, Japan. Tel: +81-6-6466-5271; Fax: +81-6-6466-5491; E-mail: koji-takemoto{at}ds-pharma.co.jp
Objectives: The aim of this study was to evaluate the efficacy and tissue concentration of AmBisome and Fungizone in murine pulmonary aspergillosis, and to investigate the localization of AmBisome at the infection site.
Methods: Mice were infected intratracheally with Aspergillus fumigatus. A single dose of each of the antifungals was administered intravenously 4 h after infection. The efficacy of the antifungal treatment was assessed by the pulmonary fungal burden at 20 h post-treatment and the survival time over 1 month. The pulmonary amphotericin B (AMB) concentration was measured until 48 h after administration. The distribution of AmBisome in the lung was evaluated using rhodamine-labelled AmBisome and an anti-AMB antibody.
Results: AmBisome at a dose of 
1 mg/kg significantly prolonged the survival time of infected mice compared with the control group. At the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in terms of increasing survival and reducing the fungal burden. The pulmonary AMB concentration of 10 mg/kg AmBisome was higher than that of 1 mg/kg Fungizone. Tissue distribution analysis showed that AmBisome was localized at the infection site in the lung, and this might explain the potent in vivo efficacy in this infection model.
Conclusions: AmBisome is localized at the infection site in the lung and consequently may fully exhibit its in vivo activity. The efficacy of AmBisome is superior to that of Fungizone against pulmonary aspergillosis.
Keywords: liposomal amphotericin B , amphotericin B deoxycholate , Aspergillus fumigatus , localization
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