[Cyclosporin A eyedrops: manufacturing, toxicity, pharmacokinetics and indications in 2000].
BACKGROUND
Cyclosporin eye-drops allow local immunoregulation without systemic side effects and is an alternate to local steroids. In this article we review specific problems of product setup and clinical studies published over the past 20 years. PRODUCT SETUP: The main problems in eye-drop preparation are sterility, pH, particles, and its lipophilic properties. Numerous excipients have been tested including oil solvents, alphacyclodextrin, collagen shields, liposomes, polyester nanocapsules, but documentation on stability of the molecule is inadequate.


RESULTS
Epithelial toxicity is well known and is probably mainly due to the excipient. No endothelial toxicity has been described in vivo. Repeated doses lead to uveal reactions in animals, which could limit the indications for intraocular diseases.


RESULTS
Bioavailability is mainly limited by the lipophilic properties. Oil excipients, the most widely used, lead to good corneal penetration but low intraocular concentrations. Cyclosporin bioavailability is improved when using hydrophilic excipients.


METHODS
Every ocular surface disease that involves cytokines is a potential indication for cyclosporine eyedrops: keratoconjunctivitis sicca, vernal keratitis, adjuvant therapy of filtering surgery, stromal herpes keratitis, immunity limbal keratitis, and Thygeson's keratitis. There is biological evidence of efficacy, and encouraging results from many studies, yet few have tested a large number of patients. A large multicenter study on dry eye is currently in progress.
Robert
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Service d'ophtalmologie, CHRU Dupuytren, 2, av. Martin Luther King, 897042 Limoges Cedex.
Leconte
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Olivé
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Ratsimbazafy
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Javerliat
M
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Adenis
J P
JP
D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D016039:Corneal Transplantation; D003320:Corneal Ulcer / Q000188:drug therapy; D016572:Cyclosporine / Q000737:chemistry / Q000493:pharmacokinetics* / Q000600:supply & distribution / Q000627:therapeutic use*; D004337:Drug Carriers; D006801:Humans; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000600:supply & distribution / Q000627:therapeutic use*; D007634:Keratitis / Q000188:drug therapy; D008081:Liposomes; D009883:Ophthalmic Solutions; D018579:Patient Selection; D014018:Tissue Distribution
D004337:Drug Carriers; D007166:Immunosuppressive Agents; D008081:Liposomes; D009883:Ophthalmic Solutions; D016572:Cyclosporine