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. 2019 Jul 1;9:9482. doi: 10.1038/s41598-019-45890-w

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Pharmacodynamics and pharmacokinetics of PC945 in an in vitro model of the human alveolus. (A) Time-dependent change of GM in lower chamber after azole-susceptible A. fumigatus infection to the upper chamber, n = 3, ***p < 0.001 vs. control (B) Concentration-dependent change of GM in lower chamber 24 h after azole-sensitive A. fumigatus (NCPF2010; ■) or azole-resistant A. fumigatus (TR₃₄/L98H; □) inoculation to the upper chamber, n = 3, **p < 0.01 vs NCPF2010 control, ^##p < 0.01 vs. L98H control (C) PC945 in cell membrane recovered 24 h after treatment to the upper chamber. (D) Correlation of PC945 cellular content with inhibition of A. fumigatus penetration to the lower chamber, (E) Retention of PC945 in the bilayer when treated for 2 h (▲) or 2 h plus 24 h washout (●), (F) PC945 in media of upper (■) and lower (▲) chamber recovered 24 h after treatment to the upper chamber.