Noxafil

Data were obtained from a prospective study by Vanstraelen et al. 12 In this study, 14 immunocompromised children aged 13 years or younger with a hematological malignancy were treated prophylactically with the posaconazole oral suspension (Noxafil, Merck, Brussels, Belgium) at a dose of 120 mg/m 2 three times daily, taken with a meal. 12 Eight blood samples were collected from each patient during one dosing interval at steady-state (after at least eight days of treatment). The study protocol was approved by the local Ethics Committee (NCT02372357). Written informed consent was obtained from each child's relative. The study was conducted in accordance with the Declaration of Helsinki.

Institute of Public Health (WIV, Brussels, Belgium) and Prof. J. Maertens (University Hospital Leuven, Belgium) and included A. flavus (B59000), A. niger (J930117), A. terreus (IHEM 5918) and A. fumigatus (B19119 and AF198-R [azole-resistant]). The isolates were cultivated on Sabouraud dextrose agar (SDA) (Lab M, U.K.) supplemented with 0.5% (w/v) chloramphenicol (Sigma-Aldrich, Diegem, Belgium). Stocks with a concentration of 5x10 6 colony forming units (cfu)/ml were prepared in RPMI-MOPS with 10% glycerol and 0.01% Tween-80 and frozen in liquid nitrogen. For the in vitro experiments, pre-titrated cryopreserved vials were used. Fresh inocula of A. fumigatus B19119 were used for the in vivo studies.
Antifungal compounds MIL, VOR (Sigma-Aldrich) and POS (Merck, Noxafil® oral formulation 40 mg/ml) were used as reference drugs. Dafra Pharma Research and Development (Turnhout, Belgium) supplied liposomal OlPC (18 mg/ml or 41.5 µM) for in vitro and in vivo use.

However, the particle size distribution for posaconazole aerosol was not reported earlier. The particle size distribution for both triazoles was determined using a previously optimized system (AeroEclipse II nebulizer with 8650D compressor operated at 40 psig). Voriconazole lyophilized powder (Vfend I.V.; Pfizer Inc., NY) or posaconazole intravenous solution (Noxafil; Merck & Co., INC., NJ) was reconstituted or diluted, respectively, to 10 mg/mL of voriconazole and 6 and 12 mg/mL of posaconazole. Sterile water for injection was used to reconstitute voriconazole, as per manufacturer's instruction, whereas posaconazole dilutions were prepared in 0.9% normal saline. Triplicate trials were performed at room temperature in a next generation impactor (MSP Corporation, MN) operated at 15 L/min to obtain parameters such as mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), percentage of respirable fraction (RF), and percentage of fine particle fraction (FPF). 18 The online calculator tool at www.mmadcalculator.com 19 was used to calculate MMAD and GSD. RF and FPF were calculated as percentage of aerosol particles <5.4 and 3.3 µm, respectively.