In Vivo Activity of Syn2869, a Novel Antifungal Triazole in Murine Models of Deep Mycosis.

T. FURUKAWA, H. SAITO, T. UJI, K. NISHIDA, F. HIGASHITANI, N. UNEMI, and H. YAMAGUCHI

Abstract: 

Syn2869, (2R, 3R)-2-(2,4- Diflourophenyly)-3-[4-{4-[2-(4-triflouromethyloxybenzyl )-2H-1,2, 4-triazole-3-one-4-yl] phenyl}piperazin-1-yl]1-(1H-1,2,4-triazole-1-yl)butan-2-ol, is an orally active broad-spectrum antifungal agent. We tested the in vivo efficacy of Syn2869 in several experimental systemic fungal infections, particularly transtracheal pulmonary infection caused by Aspergillus fumigatus in mice which had been immunosuppressed by X-ray irradiation, and compared its activity with that of hydroxypropyl--cyclodextrin formulated Itraconazole (ITCZ). When administered at a daily oral dosage of 50mg/kg for 3 successive days, Syn2869 and ITCZ prolonged the survival of Aspergillus -infected mice by 104 and 42%, respectively, as compared with untreated control animals, indicating the significantly higher efficacy of Syn2869 over ITCZ. Treatment with Syn2869 also significantly reduced fungal titers in the lung, as well as reducing the blood level of 1,3--D-glucan in the infected mice. The AUC_{0-t} values of Syn2869 and ITCZ in mice after a single oral dose of 50mg/kg were 31.3 and 13.6micro g.h/g, respectively. The higher level of Syn2869 may explain its better efficacy in the murine model of pulmonary aspergillosis. Syn2869 was also more effective than ITCZ in the treatment of experimental systemic infections caused by Candida albicans and Cryptococcus neoformans in mice. Further investigations in humans are warranted.
1998

abstract No: 

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Full conference title: 

38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th