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HY Cajucom-Uy, C Gomezperalta, L Zhou, J Theng, A Barathi, D Tan; One year pharmacokinetic study of a Cyclosporine Drug Delivery System in the Anterior Segment of Rabbit Eyes . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2233.
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Purpose: To determine the duration and tissue concentration of a sustained release Oculex Drug Delivery System (DDSTM) containing Cyclosporin A (CsA) in the anterior chamber of a rabbit model for a period of 1 year. Methods: One Oculex DDSTM containing 0.5 mg of CsA was inserted in the anterior chamber of 17 New Zealand white rabbits (34 eyes) through a clear corneal incision. Clinical slit lamp examinations were performed on days 1,7,14, and monthly for 1 year after surgery. The rabbits were sacrificed and eyes enucleated at 12 weeks and subsequently at monthly intervals up to one year. Conjunctiva, limbus, corneal epithelium, stroma and endothelium, iris, lens epithelium and lens, vitreous, retina and sclera were analysed for CsA levels by high performance liquid chromatography - mass spectrometry (HPLC-MS). Results: Corneal epithelium, stroma and endothelium displayed consistently high levels of CsA during the first 10 months.. Low to negligible amounts of CsA were found in the iris, conjunctiva, sclera, limbus, lens and retina throughout the study. Aqueous humor achieved high levels in the first 10 days ( mean= 43.55ng/ml ) and remained between 12.6 to 4.38 ng/ml during the one year period. Vitreous concentrations ranged from 1.48 to 9.64 ng/ml during the study. Sequential evaluation of remnant DDSTM pellets revealed a linear release relationship ( R2= 0.9888), with a CsA release rate of 1.15 ug/day. Conclusion: The Oculex DDSTM CsA pellet is able to provide sustained release of CsA in the anterior chamber and within all layers of the cornea tissue for up to 10 months. Potential clinical indications in humans include prophylaxis for corneal transplantation rejection, and the treatment of chronic anterior segment inflammatory diseases. Safety and toxicology studies, and evaluation of the efficacy of this device in a rabbit corneal transplantation model are currently underway.
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