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

Vet Ophthalmol. 2020 Jul;23(4):640-647. doi: 10.1111/vop.12764. Epub 2020 May 8.


Objective: 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.

Animals studied: Five healthy Thoroughbred horses.

Procedures: 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 AUC0-24 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.

Keywords: Aspergillus; horse; keratomycosis; pharmacodynamics; pharmacokinetics; tear fluid.

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*


  • Antifungal Agents
  • Voriconazole