Delivery of SAR 1118 to the retina via ophthalmic drops and its effectiveness in a rat streptozotocin (STZ) model of diabetic retinopathy (DR)

Invest Ophthalmol Vis Sci. 2010 Oct;51(10):5198-204. doi: 10.1167/iovs.09-5144. Epub 2010 May 5.

ABSTRACT

PURPOSE: 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.

METHODS: The ocular pharmacokinetics of SAR 1118 were studied in rats after a single topical dose of (14)C-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.

RESULTS: A single dose of 6.5% (14)C-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.

CONCLUSIONS: 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.

PMID:20445119 | PMC:PMC3066602 | DOI:10.1167/iovs.09-5144

Description

CONCLUSIONS: 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.

pubmed:20445119
https://pubmed.ncbi.nlm.nih.gov/20445119/?utm_source=curl&utm_medium=rss&utm_campaign=None&utm_content=1VUFS2KU_hFtBW8JwQk072MHYZ5gxZFnBkRHVr5WgfOlmKiMcV&fc=None&ff=20240712054144&v=2.18.0.post9+e462414
Published Date
2010-05-07
Associated Team Member
Invest Ophthalmol Vis Sci
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51(10):5198-204
2010
05
Vidhya R Rao, Elizabeth Prescott, Namdev B Shelke, Ruchit Trivedi, Peter Thomas, Craig Struble, Tom Gadek, Charles A O'Neill, Uday B Kompella
Approved Therapy
Investigation Type
Development Phase
Therapy Class