Clinical Feasibility and Airway Deposition of Nebulized Voriconazole in Healthy Horses

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.

Keywords: Equine; Fungal pneumonia; Fungal rhinitis; Nebulization; Pneumomycosis; Voriconazole.