Airway Deposition of Nebulized Voriconazole in Horses

Abstract

Voriconazole (VRC) is a potential treatment for pneumomycosis in horses. The objectives of this study were to determine if 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 higher in the pulmonary epithelial lining fluid than plasma. A secondary objective was to determine [VRC] in upper airways through 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 timepoints (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 post-nebulization at timepoints up to 8 hours. 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 timepoints 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 post-nebulization 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 post-nebulization showed antifungal activity. Nebulized Vfend® solution is not recommended for treatment of pneumomycosis in horses.