In Vivo Antifungal Activity of CS-758 (R-120758): III. Efficacy against Experimental Invasive Pulmonary Aspergillosis in Mice

T. FUKUOKA1, Y. KAMAI1, M. KUBOTA1, E. TSUKADA1, T. SHIBAYAMA1, T. HIROTA1, K. UCHIDA2, H. YAMAGUCHI2, S. KUWAHARA3

Author address: 

1Res. Labs., Sankyo Co., Ltd., Tokyo, Japan, 2Teikyo Univ. Inst. of Med. Mycology, Tokyo, Japan, 3Toho Univ. Sch. of Med., Tokyo, Japan.

Abstract: 

Background: CS-758 (CS) is a triazole antifungal agent with potent in vitro activity against Aspergillus species. We evaluated the efficacy of CS against experimental invasive pulmonary aspergillosis in mice and compared the efficacy with those of fluconazole (FLCZ), itraconazole (ITCZ), and amphotericin B (AMPH-B). Methods: Male DBA/2 mice (n=8) were immunosuppressed with cortisone acetate and inoculated intratracheally with 104 cells of Aspergillus fumigatus TIMM1776 strain. Treatment was started 24 hours after the inoculation and repeated once daily for 7 days. CS at 2.5, 5, and 10 mg/kg/dose, FLCZ at 80 mg/kg/dose, and ITCZ at 10 and 80 mg/kg/dose were administered orally and AMPH-B at 1.25, 2.5, and 5 mg/kg/dose was administered intraperitoneally. The mortality of the mice was recorded daily for 10 days after the inoculation. The plasma concentration of CS was measured by HPLC after a single administration of 10 mg/kg/dose to DBA/2 mouse, and the plasma concentration-time profile was simulated. Results: CS at 10 mg/kg/dose, ITCZ at 80 mg/kg/dose, and AMPH-B at 5 mg/kg/dose prolonged the survival of mice significantly (P
2001

abstract No: 

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Full conference title: 

ICAAC 41st
    • ICAAC 41st