Clinical Feasibility and Airway Deposition of Nebulized Voriconazole in Healthy Horses |
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| Institution: | 1. Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL;2. Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL;3. Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL;1. Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA;2. Department of Veterinary Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, CA;1. Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, St-Hyacinthe, Quebec, Canada;2. School of Veterinary Medicine and Animal Sciences, University of Sao Paulo, São Paulo, Brazil;3. Institute for Bioengineering of Catalonia, Barcelona, Spain;1. Division of Virology, Kimron Veterinary Institute, Bet Dagan, Israel;2. Division of Pathology, Kimron Veterinary Institute, Bet Dagan, Israel;3. Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel;1. Department of Veterinary Sciences, Biochemistry Unit, University of Messina, Polo Universitario dell’Annunziata, Messina, Italy;2. Department of Clinical and Experimental Medicine, University of Messina, Policlinico Universitario, Messina, Italy;3. Department of Veterinary Sciences, Physiology Unit, University of Messina, Polo Universitario dell’Annunziata, Messina, Italy;1. Department of Veterinary Medicine, University of Sassari, Sassari, Italy;2. Rescue Center of Wild Fauna of the Autonomous Region of Sardinia, Forestas, Italy;3. Chair of Animal Nutrition Physiology and Nutrition, University of Rostock, Rostock, Germany;4. Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy;1. Department of Agrarian Studies, Universidade Regional do Noroeste do Estado do Rio Grande do Sul, Ijuí, Rio Grande do Sul, Brazil;2. Postgraduate Program in Animal Medicine: Equine, College of Veterinary Medicine Federal University of Rio Grande do Sul – UFRGS. Av. Bento Gonçalves, Porto Alegre, Rio Grande do Sul, Brazil;3. College of Veterinary Medicine, Federal University of Rio Grande do Sul – UFRGS, Porto Alegre, Rio Grande do Sul, Brazil;4. Department of Large Animal Medicine, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil |
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| Abstract: | Voriconazole (VRC) is a potential treatment for pneumomycosis in horses. The objectives of this study were to determine if the delivery of Vfend using a Flexineb nebulizer produced clinically significant VRC] in lower airways. The hypothesis was that VRC] after delivery by nebulization would be greater in the pulmonary epithelial lining fluid than plasma. A secondary objective was to determine VRC] in upper airways through the collection of nasopharyngeal wash (NPW) samples. Voriconazole solution Vfend-6.25 mg/mL, 100 (n = 2), 200 (n = 3), 500 (n = 1) mg] was nebulized once in 6 healthy geldings. Clinical responses, duration of nebulization, and VRC] at various time points (up to 8 hours) in plasma, bronchoalveolar lavage fluid (BALF) supernatant and cell pellet, and NPW samples were recorded. Voriconazole (Vfend-6.25 mg/mL, 200 mg) was nebulized in 5 additional, healthy geldings, and VRC] was measured in NPW samples pre- and postnebulization at time points up to 8 hours. The antifungal activity of BALF and NPW samples was determined using agar disk diffusion. Concentrations of voriconazole were below detection in plasma, BALF supernatant, and cell pellets for all time points and doses except the BALF cell pellet (0.4 μg/g) immediately after nebulization of 500 mg. For 5 horses, administered 200 mg of Vfend, mean VCR] in NPW at the end of nebulization and 1, 6, and 8 hours postnebulization were: 30.8 ± 29, 1.0 ± 0.84, 0.2 ± 0.19, and 0.34 ± 0.67 μg/mL, respectively. Only NPW samples obtained immediately postnebulization showed antifungal activity. A nebulized Vfend solution is not recommended for the treatment of pneumomycosis in horses. |
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| Keywords: | Equine Voriconazole Nebulization Pneumomycosis Fungal pneumonia Fungal rhinitis |
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