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.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication Date: 2020-09-03 PubMed ID: 33077094DOI: 10.1016/j.jevs.2020.103246Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The study focused on the potential use of voriconazole, a drug used against fungal infections, as a treatment for lung infections in horses. The researchers particularly wanted to determine if administering this drug through nebulization would result in a higher concentration in the pulmonary epithelial lining fluid than the plasma. The conclusion was that the drug did not reach sufficient concentrations in the targeted areas; hence, its use in this manner is not recommended.
Objective of the Study
- The primary objective of this research was to determine whether delivering voriconazole via a Flexineb nebulizer would result in desirable concentration of the drug in horses’ lower airways. Apart from this, investigating the concentration of the voriconazole in horses’ upper airways was a secondary aim.
Research Hypothesis
- The researchers hypothesized that the concentration of voriconazole achieved in the pulmonary epithelial lining fluid would be greater than its plasma concentration when delivered via nebulization.
Research Methodology
- A solution of voriconazole [Vfend-6.25 mg/mL], in amounts of 100 (for 2 horses), 200 (for 3 horses), and 500 mg (for 1 horse), was nebulized for 6 healthy geldings. Observations included clinical responses, nebulization duration, and voriconazole concentration at various time points in plasma, bronchoalveolar lavage fluid, and nasopharyngeal wash samples.
- A second part of the study involved nebulizing an additional five healthy geldings with 200 mg of Vfend. Again, the concentration of voriconazole in nasopharyngeal wash samples was measured before and after nebulization over a span of 8 hours. The antifungal activity of the bronchoalveolar lavage fluid and nasopharyngeal wash samples was determined using agar disk diffusion.
Research Findings
- The concentrations of voriconazole were generally below detection levels in plasma, bronchoalveolar lavage fluid supernatants, and cell pellets across all time points regardless of the dose used, except in the case of the bronchoalveolar lavage fluid cell pellet where 500 mg of Vfend had been nebulized.
- In the second part of the study, nasopharyngeal wash samples showed gradually decreasing concentrations of the drug, and only samples procured immediately after nebulization displayed antifungal activities.
Conclusion
- Based on the collected data, the researchers ultimately concluded that the use of a nebulized Vfend solution is not recommended for the treatment of pneumomycosis in horses due to the inadequacy of drug concentrations in the targeted areas.
Cite This Article
APA
Sierra-Rodriguez T, Groover ES, Lascola KM, Mora-Pereira M, Lee YH, Duran SH, Ravis WR, Spangler E, Hathcock T, Wooldridge AA.
(2020).
Clinical Feasibility and Airway Deposition of Nebulized Voriconazole in Healthy Horses.
J Equine Vet Sci, 94, 103246.
https://doi.org/10.1016/j.jevs.2020.103246 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL.
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL.
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL.
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL.
- Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL.
- Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL. Electronic address: aaw0002@auburn.edu.
MeSH Terms
- Animals
- Antifungal Agents / therapeutic use
- Body Fluids
- Bronchoalveolar Lavage Fluid
- Feasibility Studies
- Horses
- Male
- Voriconazole
Citations
This article has been cited 3 times.- Egli P, Boone L, Huber L, Higgins C, Gaonkar PP, Arrington J, Naskou MC, Peroni J, Gordon J, Lascola KM. Pilot study characterizing a single pooled preparation of equine platelet lysate for nebulization in the horse. Front Vet Sci 2024;11:1488942.
- Toner S, Leguillette R, Israel J, Legge C, Samani ARE, Kavanagh M, Goodmanson M. Long-term follow-up of laryngeal Rhinosporidium seeberi diagnosed by PCR and treated with laser ablation and voriconazole nebulization in a retired thoroughbred polo horse. Can Vet J 2024 Jul;65(7):667-674.
- Mahalingam-Dhingra A, Mazan MR, Bedenice D, Ceresia M, Minuto J, Deveney EF. A CONSORT-guided, randomized, double-blind, controlled pilot clinical trial of inhaled lidocaine for the treatment of equine asthma. Can J Vet Res 2022 Apr;86(2):116-124.
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