Cyclosporin A eyedrops: manufacturing, kinetics and indications in 2000

Introduction: Cyclosporin eye-drops allow local immunoregulation without sy stemic 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 te sted including oil solvents, alphacyclodextrin, collagen shields, liposomes , polyester nanocapsules, but documentation on stability of the molecule is inadequate. Toxicity: Epithelial toxicity is well known and is probably mainly due to t he 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. Pharmacokinetics: Bioavailability is mainly limited by the lipophilic prope rties. Oil excipients, the most widely used, lead to good corneal penetrati on but low intraocular concentrations. Cyclosporin bioavailability is impro ved when using hydrophilic excipients. Indications: Every ocular surface disease that involves cytokines is a pote ntial indication for cyclosporine eyedrops : keratoconjunctivitis sicca, ve rnal keratitis, adjuvant therapy of filtering surgery, stromal herpes kerat itis, immunity limbal keratitis, and Thygeson's keratitis. There is biologi cal evidence of efficacy, and encouraging results from many studies, yet fe w have tested a large number of patients. A large multicenter study on dry eye is currently in progress.