P7 Efficacy of antifungal therapy with inhaled azole against murine invasive pulmonary aspergillosis with ITCZ-low susceptible Aspergillus fumigatus

Hirano, Kohji; Izumikawa, K.; Morinaga, Y.; Kurihara, Shintaro; Nakamura, Shigetaka; Imamura, Yoshifumi; Miyazaki, Tatsuya; Tsukamoto, Masako; Kakeya, Hiroshi

doi:10.1016/s0924-8579(13)70252-8

Cited by 2 publications

(2 citation statements)

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“…McConville et al demonstrated previously that single-dose nebulized itraconazole maintained high concentrations in the lung in mice for more than 24 h ( 18 ), and this was also demonstrated in rats ( 19 ). Furthermore, the survival rates of the group of mice receiving nebulized itraconazole were significantly higher than those of the group of mice receiving oral itraconazole administration ( 20 ). Since those reports, new formulations of itraconazole for topical treatment, such as nanoparticles ( 21 , 22 ), polymeric micelles ( 23 ), itraconazole-loaded nanostructured lipid carriers ( 24 ), and dry powder ( 25 ), have been developed, although the in vivo antifungal activities of these inhaled products have not been reported formally.…”

Section: Introductionmentioning

confidence: 83%

In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice

Kimura

Nakaoki

Colley³

et al. 2017

Antimicrob Agents Chemother

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PC945 is a novel triazole optimized for lung delivery, and the objective of this study is to determine the effects of intranasally dosed PC945 on Aspergillus fumigatus infection and associated biomarkers in immunocompromised mice. PC945, posaconazole, or voriconazole was administered intranasally once daily on days 0 to 3 (early intervention) or days 1 to 3 (late intervention) postinfection in temporarily neutropenic A/J mice infected intranasally with A. fumigatus, and bronchoalveolar lavage fluid (BALF) and serum were collected on day 3. The effects of extended prophylaxis treatment (daily from days −7 to +3 or days −7 to 0) were also compared with those of the shorter treatment regimens (days −1 to +3 or days −1 and 0). Early and late interventions with PC945 (2.8 to 350 μg/mouse; approximately 0.11 to ∼14 mg/kg of body weight) were found to inhibit lung fungal loads and to decrease the concentrations of galactomannan (GM) in both BALF and serum as well as several biomarkers in BALF (interferon gamma [IFN-γ], interleukin-17 [IL-17], and malondialdehyde) and serum (tumor necrosis factor alpha [TNF-α] and IL-6) in a dose-dependent manner and were >3- and >47-fold more potent than intranasally dosed posaconazole and voriconazole, respectively. Furthermore, extended prophylaxis with low-dose PC945 (0.56 μg/mouse; 0.022 mg/kg) was found to inhibit fungal loads and to decrease the concentrations biomarkers more potently than did the shorter treatment regimens. Thus, PC945 dosed intranasally once daily showed potent antifungal effects, and the effects of PC945 accumulated upon repeat dosing and were persistent. Therefore, PC945 has the potential to be a novel inhaled therapy for the treatment of A. fumigatus infection in humans.

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Section: Introductionmentioning

confidence: 83%

In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice

Kimura

Nakaoki

Colley³

et al. 2017

Antimicrob Agents Chemother

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“…demonstrated that a single dose of nebulised itraconazole maintained high concentrations in lung in mice for more than 24 hours and it has also been demonstrated in rats . Furthermore the survival rates of the group of mice receiving nebulised itraconazole were significantly higher than the group of mice receiving oral itraconazole administration . Posaconazole, the most potent triazole, has longer tissue retention than itraconazole or voriconazole, but topical treatment of posaconazole, as a potential option for the treatment, has not been tested in vivo.…”

Section: Introductionmentioning

confidence: 99%

Effects of intranasally dosed posaconazole on fungal load and biomarkers in Aspergillus fumigatus infected immunocompromised mice

Kimura

Nakaoki

Nishimoto

et al. 2017

Mycoses

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SummaryAlthough anti-fungal triazoles are dosed orally or systemically for Aspergillus fumigatus infection, systemic adverse events and limited exposure of the lung cavity would make a topical treatment for the lung an attractive option. In this study, we examined the effects of intranasally dosed posaconazole on survival rates and biomarkers in K E Y W O R D SAspergillus fumigatus, galactomannan, intranasal treatment, itraconazole resistant, posaconazole

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P7 Efficacy of antifungal therapy with inhaled azole against murine invasive pulmonary aspergillosis with ITCZ-low susceptible Aspergillus fumigatus

Cited by 2 publications

References 0 publications

In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice

In Vivo Biomarker Analysis of the Effects of Intranasally Dosed PC945, a Novel Antifungal Triazole, on Aspergillus fumigatus Infection in Immunocompromised Mice

Effects of intranasally dosed posaconazole on fungal load and biomarkers in Aspergillus fumigatus infected immunocompromised mice

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