Voriconazole orally for fungal keratitis and corneal ulceration

One of the most difficult medical situations in horses is rapidly progressive corneal ulceration with fungi frequently the cause. NB that bacteria also can be a common cause making early diagnostic work important, see the article. The rapid rate of progression in combination with the difficulty of the needed repeated frequent treatment of the eye can be daunting and expensive. Here is an amazing solution to the treatment of corneal fungi infections, and in particular Aspergillus species, using voriconazole orally in the horse. Voriconazole turns out to be readily available in the body after oral administration and well tolerated at doses above those that appear to be effective at creating a rapid and significant antifungal concentrations in the eye. Rarely does all of this fall together so neatly. This is not cheap however as voriconazole bought at a discount pharmacy with a Good Rx card will still run you 25 to 30 dollars a day (Sept 2021) for a standard to large size horse.
DrO

Vet Ophthalmol. 2020 May 8.
Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic-pharmacodynamic analysis of tear fluid following oral administration.
Tamura N1,2, Okano A1, Kuroda T1, Niwa H2, Kusano K1, Matsuda Y1, Fukuda K1, Mita H2, Nagata S3.

Author information:
1. Miho Training Center, Japan Racing Association, Racehorse Hospital, Ibaraki, Japan.
2. Japan Racing Association, Equine Research Institute, Tochigi, Japan.
3. Laboratory of Racing Chemistry, Tochigi, Japan.
Abstract
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.