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B. C. Gilger, C. P. Moore, K. Narfstrom, J. Liu, C. Lawson, T. Cacek, E. Anglade, P. Velagaleti; Preclinical Acute Toxicity and Pharmacokinetics of Episcleral LX201 Implants in Rabbits. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1964.
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The purpose of this study was to determine acute tolerability, toxicity, and ocular tissue distribution of cyclosporine (CsA) from the episcleral LX201 implant, a device in development for the treatment of high-risk corneal transplantation.
Twenty-four, adult, normal New Zealand White rabbits were divided into 3 groups, which each received 1 - 3 CsA (30%)-containing silicone implants (LX201), silicone implants only, or no treatment. Both the drug-free and CsA-containing silicone implants were placed surgically in the superior episcleral space in both eyes. Ophthalmic examinations, electroretinography (ERG), and CBC and serum chemistry profiles were performed pretreatment and at 7 and 14 days after implantation. Whole blood pharmacokinetic (PK) samples were collected pretreatment and on days 1, 2, 4, 6, 8, 10, 12, and 14 after implantation. Euthanasia with complete necropsy was performed in all rabbits at 14 days. One eye from each rabbit was processed for histopathology and the other was processed for ocular tissue CsA distribution.
LX201 implants did not extrude from the eyes at any point during the study. No ocular or periocular abnormalities were noted on complete ocular examinations, except for mild conjunctival hyperemia at the site of the surgery. There were no statistical differences in ERG parameters among treatment groups and no abnormalities were observed on gross necropsy or ocular histopathology, other than expected mild fibrosis and an occasional inflammatory cell at the episcleral implant site. The only significant serum chemistry abnormality was an elevation of LDH at day 7 in rabbits with 3 LX201 implants, likely a result of surgical stress. Whole blood CsA levels (PK) were 0.453-2.02 ng/ml in LX201 implanted rabbits on days 2 -14.
LX201 implants were tolerated well in rabbits (up to 3 per eye) and no extrusions occurred. Evidence of acute toxicity was not observed in any of the treatment groups. These results support the continued evaluation of episcleral LX201 ocular implants for prevention of rejection in high-risk corneal transplantation.
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