Abstract
Purpose: :
To determine and correlate the ocular penetration and distribution of dexamethasone using results from a clinical study with cataract patients and a rabbit model that simulates dosing in the human eye, comparing TobraDex® ophthalmic suspension to a new formulation containing half the concentration of dexamethasone in a novel suspension technology.
Methods: :
In the clinical study, 957 patients received one drop of either TobraDex® ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%) or TobraDex ST suspension (tobramycin 0.3%, dexamethasone 0.05%) at various time points prior to cataract surgery. Clinical samples of the aqueous humor were collected at the time of surgery. In the rabbit model, anesthetized rabbits were given a single topical dose of either suspension followed by a 60 minute controlled period that simulated the human eye with manual blinking (4 blinks/min) and supplementary tearing (2 µL/min). Tear samples were collected every 5 minutes, and after euthanasia, tissue samples were collected at 60 minutes. Dexamethasone concentrations were quantified using HPLC.
Results: :
In the clinical study, after 60 minutes, the ratio of dexamethasone levels in the aqueous humor was 1.18 in favor of the new formulation (20.7 versus 17.5 ng/mL). In the rabbit model, the mean concentrations of dexamethasone [µg/mL or µg/g ± SE (n=4)] at 60 minutes were as follows: in the aqueous humor 0.77± 0.08 versus 0.64 ± 0.03 (ratio 1.20); in the conjunctiva 1.2 ± 0.3 versus 0.8 ± 0.2 (ratio 1.5); in the cornea 2.8 ± 0.5 versus 1.6 ± 0.4 (ratio 1.75); in the sclera 0.77 ± 0.08 versus 0.64 ± 0.03 (ratio 1.2); and in the iris-ciliary body 2.1 ± 0.3 versus 1.6 ± 0.3 (ratio 1.3). In the rabbit tears, 10 minutes after dosing, the dexamethasone levels were 37 ± 11 versus 11 ± 6 (ratio 3.4).
Clinical Trial: :
www.clinicaltrials.gov NCT00473070
Keywords: cataract • corticosteroids • aqueous