title: Activity and Safety of Inhaled Itraconazole Nanosuspension in a Model Pulmonary Aspergillus fumigatus Infection in Inoculated Young Quails.
abstract: Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis.
authors: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL-20033, Lublin, Poland, piotr.wlaz@umcs.lublin.pl.
authors: Piotr
authors: P
authors: Wlaź
authors: Sebastian
authors: S
authors: Knaga
authors: Kornel
authors: K
authors: Kasperek
authors: Aleksandra
authors: A
authors: Wlaź
authors: Ewa
authors: E
authors: Poleszak
authors: Grażyna
authors: G
authors: Jeżewska-Witkowska
authors: Stanisław
authors: S
authors: Winiarczyk
authors: Elżbieta
authors: E
authors: Wyska
authors: Thorsten
authors: T
authors: Heinekamp
authors: Chris
authors: C
authors: Rundfeldt
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001232:Aspergillus fumigatus / Q000187:drug effects*; D003370:Coturnix; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D017964:Itraconazole / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage* / Q000009:adverse effects; D055732:Pulmonary Aspergillosis / Q000188:drug therapy* / Q000473:pathology; D012720:Severity of Illness Index; D016019:Survival Analysis; D013535:Suspensions / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D013535:Suspensions; D017964:Itraconazole