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Antimicrobial Agents and Chemotherapy, March 2000, p. 619-621, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Efficacy of FK463, a New Lipopeptide Antifungal Agent, in Mouse Models of Pulmonary Aspergillosis

Satoru Matsumoto,1 Yoshimi Wakai,1 Toru Nakai,1 Kazuo Hatano,1 Tomoe Ushitani,1 Fumiaki Ikeda,1,* Shuichi Tawara,1 Toshio Goto,1 Fumio Matsumoto,2 and Shogo Kuwahara3

Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Kashima, Yodogawa-ku, Osaka 532-8514,1 Kanagawa Prefectural Nursing and Hygienic School Hospital, 1-6, Shiomidai, Isogo-ku, Yokohama 235-0022,2 and Toho University School of Medicine, Ohmori Nishi, Ohta-ku, Tokyo 143-8540,3 Japan

Received 3 May 1999/Returned for modification 26 July 1999/Accepted 10 December 1999

The efficacy of FK463, a novel water-soluble lipopeptide, was evaluated in mouse models of pulmonary aspergillosis and was compared with that of amphotericin B (AMPH-B). In the pulmonary aspergillosis models induced by intranasal inoculation, FK463 exhibited good efficacy, with 50% effective doses in the range of 0.26 to 0.51 mg/kg of body weight; these values were comparable to those of AMPH-B. In an Aspergillus target organ assay with immunosuppressed mice, under conditions of constant plasma levels of FK463, using a subcutaneously implanted osmotic pressure pump, a significant reduction in viable fungal cells was observed at plasma FK463 levels of 0.55 to 0.80 µg/ml or higher. We conclude that FK463 is highly effective in the treatment of pulmonary aspergillosis in this animal model. These results indicate that FK463 may be a potent parenterally administered antifungal agent for pulmonary aspergillosis.

* Corresponding author. Mailing address: Department of Infectious Diseases, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 1-6, 2-Chome, Kashima, Yodogawa-Ku, Osaka 532-8514, Japan. Phone: 81-6-6390-1158. Fax: 81-6-6304-5367. E-mail: fumiaki_ikeda{at}po.fujisawa.co.jp.

Antimicrobial Agents and Chemotherapy, March 2000, p. 619-621, Vol. 44, No. 3
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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