Efficacy of TAK-457, a novel intravenous triazole, against invasive pulmonary Aspergillosis in neutropenic mice. |
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| Authors: | Ryogo Hayashi Naomi Kitamoto Yuji Iizawa Takashi Ichikawa Katsumi Itoh Tomoyuki Kitazaki Kenji Okonogi |
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| Affiliation: | Pharmacology Research Laboratories II, Takeda Chemical Industries, Ltd., Osaka, Japan. Hayashi_Ryogo@takeda.co.jp |
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| Abstract: | TAK-457 is an injectable prodrug of TAK-456, which is a novel oral triazole compound with potent antifungal activity. The in vivo efficacy of TAK-457 was evaluated in two models of invasive pulmonary aspergillosis with CDF(1) mice and CBA/J mice with transient neutropenia induced by cyclophosphamide. Against the infection in CDF(1) mice, treatment with 10 mg of TAK-457 and 1 mg of amphotericin B/kg reduced the fungal burden in lungs and rescued all mice. In the infection model with CBA/J mice, TAK-457 at a dose of 10 mg/kg significantly prolonged the survival time of mice, showing significant reduction of lung chitin levels and the plasma beta-D-glucan levels. On the other hand, amphotericin B at 1 mg/kg which was a maximum tolerable dose showed slight but not significant prolongation of survival time of mice, although it also reduced the lung chitin levels and the plasma beta-D-glucan levels to a lower extent but still significantly. These results suggest that TAK-457 is a promising candidate for development for the treatment of invasive aspergillosis in humans. |
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