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Veterinary ophthalmology2020; 23(4); 640-647; doi: 10.1111/vop.12764

Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic-pharmacodynamic analysis of tear fluid following oral administration.

Abstract: To clarify the detailed pharmacokinetics (PK) of orally administered voriconazole in tear fluid (TF) of horses for evaluating the efficacy of voriconazole secreted into TF against equine keratomycosis. Methods: Five healthy Thoroughbred horses. Methods: Voriconazole was administrated through a nasogastric tube to each horse at a single dose of 4.0 mg/kg. TF and blood samples were collected before and periodically throughout the 24 hours after administration. Voriconazole concentrations in plasma and TF samples were analyzed using liquid chromatography-electrospray tandem-mass spectrometry. The predicted voriconazole concentration in both samples following multiple dosing every 24 hours was simulated by the superposition principle. Results: The mean maximum voriconazole concentrations in plasma and TF were 3.3 μg/mL at 1.5 h and 1.9 μg/mL at 1.6 h, respectively. Mean half-life in both samples were 16.4 and 25.2 h, respectively. The ratio of predicted AUC at steady state in TF (51.3 μg∙h/mL) to previously published minimum inhibitory concentration (MIC) of Aspergillus and Fusarium species was >100 and 25.7, respectively. Conclusions: This study demonstrated the detailed single-dose PK of voriconazole in TF after oral administration and simulated the predicted concentration curves in a multiple oral dosing. Based on the analyses of PK-PD, the simulation results indicated that repeated oral administration of voriconazole at 4.0 mg/kg/d achieves the ratio of AUC to MIC associated with treatment efficacy against Aspergillus species. The detailed PK-PD analyses against pathogenic fungi in TF can be used to provide evidence-based medicine for equine keratomycosis.
© 2020 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.
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Publication Date: 2020-05-08 PubMed ID: 32383526PubMed Central: PMC7496923DOI: 10.1111/vop.12764Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the efficiency of a drug named voriconazole in treating horse eye infections known as equine keratomycosis. By studying how the drug moves and behaves in the horse’s body after oral administration, the research provides evidence suggesting that repeated dosages are effective in treating infections caused by a type of fungus.

Methodology

  • The study involved five healthy Thoroughbred horses, in which voriconazole was administered orally at a dosage of 4.0 mg/kg.
  • Both tear fluid and blood samples were collected from the horses before and after the drug administration for 24 hours.
  • The collected samples were then analyzed using a sophisticated technique called liquid chromatography-electrospray tandem-mass spectrometry. This procedure allowed the researchers to determine the concentration of voriconazole in the plasma and tear fluid.
  • The researchers predicted the level of voriconazole in these samples after multiple doses in a 24-hour period using a mathematical calculation known as the superposition principle.

Results

  • The experiment revealed that the highest concentrations of voriconazole in blood and tear fluid occurred 1.5 hours and 1.6 hours after drug administration, respectively, with mean maximum concentrations of 3.3 μg/mL in plasma and 1.9 μg/mL in tear fluid.
  • The study also found the half-life of the drug, which is the time it takes for the drug concentration to decrease by half, was 16.4 hours in plasma and 25.2 hours in tear fluid.
  • The predicted concentration of voriconazole in tear fluid (51.3 μg∙h/mL) was found to be significantly larger than the minimum inhibitory concentration (MIC) needed to prevent the growth of Aspergillus and Fusarium fungi, meaning the drug was effectively killing these organisms.

Conclusions

  • The study provided detailed information about the pharmacokinetics (behaviour of the drug in the body) of voriconazole in tear fluid after a single oral dose, as well as projected concentrations with multiple dosage.
  • Based on these analyses, the study concluded that repeated oral administration of voriconazole at 4.0 mg/kg/d should be effective against Aspergillus species.
  • This research provides evidence-based guidance for using voriconazole in treating equine keratomycosis.

Cite This Article

APA
Tamura N, Okano A, Kuroda T, Niwa H, Kusano K, Matsuda Y, Fukuda K, Mita H, Nagata S. (2020). Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic-pharmacodynamic analysis of tear fluid following oral administration. Vet Ophthalmol, 23(4), 640-647. https://doi.org/10.1111/vop.12764

Publication

Veterinary ophthalmology
ISSN: 1463-5224
NlmUniqueID: 100887377
Country: England
Language: English
Volume: 23
Issue: 4
Pages: 640-647

Researcher Affiliations

Tamura, Norihisa
  • Miho Training Center, Japan Racing Association, Racehorse Hospital, Ibaraki, Japan.
  • Japan Racing Association, Equine Research Institute, Tochigi, Japan.
Okano, Atsushi
  • Miho Training Center, Japan Racing Association, Racehorse Hospital, Ibaraki, Japan.
Kuroda, Taisuke
  • Miho Training Center, Japan Racing Association, Racehorse Hospital, Ibaraki, Japan.
Niwa, Hidekazu
  • Japan Racing Association, Equine Research Institute, Tochigi, Japan.
Kusano, Kanichi
  • Miho Training Center, Japan Racing Association, Racehorse Hospital, Ibaraki, Japan.
Matsuda, Yoshikazu
  • Miho Training Center, Japan Racing Association, Racehorse Hospital, Ibaraki, Japan.
Fukuda, Kentaro
  • Miho Training Center, Japan Racing Association, Racehorse Hospital, Ibaraki, Japan.
Mita, Hiroshi
  • Japan Racing Association, Equine Research Institute, Tochigi, Japan.
Nagata, Shunichi
  • Laboratory of Racing Chemistry, Tochigi, Japan.

MeSH Terms

  • Administration, Oral
  • Animals
  • Antifungal Agents / administration & dosage
  • Antifungal Agents / pharmacokinetics
  • Antifungal Agents / pharmacology
  • Antifungal Agents / therapeutic use
  • Area Under Curve
  • Aspergillus / drug effects
  • Eye Infections, Fungal / drug therapy
  • Eye Infections, Fungal / veterinary
  • Female
  • Horse Diseases / blood
  • Horse Diseases / drug therapy
  • Horses / metabolism
  • Male
  • Microbial Sensitivity Tests
  • Tears / metabolism
  • Voriconazole / administration & dosage
  • Voriconazole / pharmacokinetics
  • Voriconazole / pharmacology
  • Voriconazole / therapeutic use

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Citations

This article has been cited 1 times.
  1. Bowden AC, Allbaugh RA, Smith JS, Mochel JP, Sebbag L. Kinetics and minimal inhibitory concentrations of ceftiofur in tear film following extended-release parenteral administration (Excede(®)) in dogs. Front Vet Sci 2022;9:975113.
    doi: 10.3389/fvets.2022.975113pubmed: 36213401google scholar: lookup
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