%0 Journal Article
%A Rao, Vidhya R.
%A Prescott, Elizabeth
%A Shelke, Namdev B.
%A Trivedi, Ruchit
%A Thomas, Peter
%A Struble, Craig
%A Gadek, Tom
%A O'Neill, Charles A.
%A Kompella, Uday B.
%T Delivery of SAR 1118 to the Retina via Ophthalmic Drops and its Effectiveness in a Rat Streptozotocin (STZ) Model of Diabetic Retinopathy (DR)
%B Investigative Ophthalmology & Visual Science
%D 2010
%R 10.1167/iovs.09-5144
%J Investigative Ophthalmology & Visual Science
%V 51
%N 10
%P 5198-5204
%@ 1552-5783
%X    To determine the pharmacokinetics of SAR 1118, a small-molecule antagonist of leukocyte function-associated antigen (LFA)-1, after administration of ophthalmic drops in normal rats, and to determine its pharmacologic activity by assessing the inhibition of retinal leukostasis and vascular leakiness in a streptozotocin (STZ)-induced diabetic retinopathy model.    The ocular pharmacokinetics of SAR 1118 were studied in rats after a single topical dose of 14C-SAR 1118 (1 mg/eye; 40 μCi; 15.5 μL). SAR 1118 concentration time profiles in plasma and ocular tissues were quantified by liquid scintillation counting (LSC). The pharmacologic activity of SAR 1118 eye drops administered thrice daily for 2 months at 1% (0.3 mg/eye/d) and 5% (1.5 mg/eye/d) was assessed in an STZ-induced diabetic rat model by determining retinal leukostasis and blood–retinal barrier breakdown. Diabetic rats treated with periocularly administered celecoxib microparticles served as the positive control, and vehicle-treated rats served as the negative control.    A single dose of 6.5% 14C-radiolabeled SAR 1118 ophthalmic drops delivered retinal drug levels greater than 1 μM in less than 30 minutes and sustained levels greater than 100 nM for 8 hours. SAR 1118 eye drops significantly reduced leukostasis and blood–retinal barrier breakdown in a dose-dependent manner.    SAR 1118 ophthalmic drops administered thrice daily deliver therapeutic levels of SAR 1118 in the retina and can alleviate the retinal complications associated with diabetes.  
%[ 3/7/2021
%U https://doi.org/10.1167/iovs.09-5144