Intrapulmonary Posaconazole Penetration at the Infection Site in an Immunosuppressed Murine Model of Invasive Pulmonary Aspergillosis Receiving Oral Prophylactic Regimens

Adequate penetration to the infection/colonization site is crucial to attain optimal efficacy of posaconazole against Aspergillus fumigatus diseases. We evaluated posaconazole exposure in pulmonary epithelial lining fluid (ELF) in a murine model of invasive pulmonary aspergillosis. The posaconazole exposure (area under the plasma concentration-time curve from time zero to 24 h postinfusion [AUC0-24]) in ELF was 20% to 31% of that in plasma for total drug after the third dose, and the relationship between plasma and ELF exposure was linear (r(2) = 0.97, P = 0.016).