Penetration of topically administered dexamethasone disodium phosphate and prednisolone acetate into the normal equine ocular fluids

Abstract

Background: Topical dexamethasone and prednisolone are currently the mainstay treatment for equine ophthalmic inflammatory diseases, such as equine recurrent uveitis. Comparative pharmacokinetic studies in horses are lacking and current guidelines are mainly based on empirical data and extrapolation from other species.

Objectives: To investigate the penetration and local concentrations of topically applied dexamethasone and prednisolone in normal equine ocular fluids and serum.

Study design: Prospective randomised experimental pharmacokinetic study.

Methods: Twenty-one Shetland ponies without ophthalmic disease were treated bilaterally topically every 2 hours during 24 hours to obtain steady state drug concentrations. One eye was treated with 0.15 mg of dexamethasone disodium phosphate (0.1%), and the other eye was simultaneously treated with 1.5 mg of prednisolone acetate (1%). Serum samples were taken prior to the induction of general anaesthesia. Aqueous and vitreous humour samples were taken during euthanasia at time points after administration of the last dose (t = 5 min, t = 15 min, t = 30 min, t = 60 min, t = 90 min, t = 120 min, t = 180 min). Each pony was randomly assigned to one time point, and three ponies were sampled per time point. Dexamethasone and prednisolone concentrations were measured by liquid chromatography-mass spectrometry.

Results: The mean dexamethasone concentration in aqueous humour was 32.4 ng/mL (standard deviation [SD] 10.9) and the mean prednisolone concentration was 321.6 ng/mL (SD 96.0). In the vitreous and in serum samples concentrations of both corticosteroids were below the limit of detection (LOD 2.5 ng/mL).

Main limitations: The study group was limited to subjects without evidence of current ophthalmic disease. A limited number of time points were measured.

Conclusions: Potentially effective dexamethasone and prednisolone concentrations were measured in the anterior chamber, but vitreal concentrations were negligible. Systemic uptake was low. Therefore, treatment with only topically administered corticosteroids is deemed insufficient in horses in cases of posterior uveitis. Further studies evaluating other routes of administration are warranted.

Keywords: corticosteroids; drug dosing interval; horse; liquid chromatography-mass spectrometry; ophthalmic; topical administration.

FIGURE 1

Plot of the DEX (blue) and PRED (green) concentrations in aqueous humour after repeated topical administration of dexamethasone disodium phosphate (0.1%) and prednisolone acetate (1%) every 2 h for 24 h. Three ponies were randomly assigned to each time point (t = 5, t = 15, t = 30, t = 60, t = 90, t = 120, t = 180 min); The box indicates the standard deviation; the small dots the three concentrations measured per time point; the big dot the mean concentration of the three samples; the horizontal line indicates the median