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Vincenzo Papa, Elena Solfato, Claudine Civiale; Delivery Of Dexamethasone To The Posterior Segment Of The Eye Using An Eye Gel Formulation. Invest. Ophthalmol. Vis. Sci. 2012;53(14):471.
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Corticosteroids are valuable drugs in the management of macular edema (ME) but therapeutic concentrations in the retina can be usually achieved only after invasive injections, making the use of topical corticosteroids not suitable for the treatment of ME. We describe herein the PK results obtained in rabbits after topical administration of a gel-based delivery system containing 1% xanthan gum and 0.15% dexamethasone phosphate (DP), a water soluble prodrug of dexamethasone (D).
A single dose of 50 µl of 0.15% DP gel (Etacortilen Gel) was applied to one eye of pigmented rabbits (n=24). D levels were measured by LC/MS-MS in aqueous humour (AH), vitreous humour (VH) and retina/choroid (R/C) of both eyes after 15, 30, 60, 120, 180 and 240 min. CMAX and AUCALL were calculated for each tissue. Data obtained from control eyes were considered expression of systemic absorption.
CMAX (mean ±SE): 83.72 ± 10.64 (study eye) vs. 0 (control eye) ng/ml in the AH, 1.76 ± 0.59 vs. 4.24 ± 1.89 ng/g in the VH and 67.79 ± 22.73 vs. 39.98 ± 9.97 ng/g in the R/C. AUCALL (mean ±SE): 178.92 ± 17.08 (study eye) vs. 0 (control eye) hr*ng/ml in the AH, 1.88 ± 0.38 vs. 6.19 ± 1.25 hr*ng/g in the VH and 129.92 ± 16.81 vs. 77.14± 9.02 hr*ng/g in the R/C. In the R/C the AUCALL in study eyes was statistically significant higher (p<0.01, Student t test) than that in control eyes.
A single topical administration of DP gel is able to deliver effective concentrations of D to the posterior segment of the eye through both systemic and topical absorption. Topical absorption across the conjunctiva and the sclera accounted for about 40% of the D reaching the posterior part of the eye. Since D levels found in the R/C are sufficient to reduce central macular thickness in patients with diabetic ME (Tanito IOVS 2011), this eye gel formulation may be useful as adjuvant topical treatment of ME, obviating any concerns associated with more invasive routes.
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