Abstract | PURPOSE: METHODS: Episcleral cyclosporine implants were manufactured with a silicone-based matrix design, and in vitro release rates were determined. Preclinical evaluation included toxicology (clinical examination, serial electroretinography, and histopathology) in normal rabbits and dogs, pharmacokinetics in normal rabbits, and pharmacodynamics in a canine model of aqueous tear deficiency and keratoconjunctivitis sicca. RESULTS: The cyclosporine implants showed sustained release of drug over time with in vitro assays. Histopathology showed normal ocular tissues in both dogs and rabbits 6 months after implantation. The cyclosporine implant produced lacrimal gland drug levels 1 to 2 log units higher than those reported with a variety of topical cyclosporine formulations and oral administration. The cyclosporine implant was effective in a canine model of keratoconjunctivitis sicca, with all animals able to discontinue topical cyclosporine and maintain normal Schirmer scores over a 6-month follow-up. CONCLUSIONS:
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Authors | Hyuncheol Kim, Karl G Csaky, Brian C Gilger, James P Dunn, Susan S Lee, Marcus Tremblay, Francisco de Monasterio, Ginger Tansey, Peng Yuan, Peter M Bungay, Robert J Lutz, Michael R Robinson |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 46
Issue 2
Pg. 655-62
(Feb 2005)
ISSN: 0146-0404 [Print] United States |
PMID | 15671296
(Publication Type: Journal Article)
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Chemical References |
- Drug Implants
- Immunosuppressive Agents
- Cyclosporine
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Topics |
- Animals
- Biological Availability
- Cyclosporine
(pharmacokinetics, pharmacology, toxicity)
- Dogs
- Drug Evaluation, Preclinical
- Drug Implants
- Electroretinography
(drug effects)
- Eye
(metabolism, pathology)
- Female
- Graft vs Host Disease
(pathology, prevention & control)
- Immunosuppressive Agents
(pharmacokinetics, pharmacology, toxicity)
- Keratoconjunctivitis
(drug therapy, pathology)
- Male
- Rabbits
- Retina
(drug effects)
- Safety
- Sclera
(drug effects, metabolism, pathology)
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