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March 1996

Evaluation of a Delivery System Providing Long-term Release of Cyclosporine

Author Affiliations

From the Department of Ophthalmology, Duke University, Durham, NC (Drs Pearson and Jaffe); Department of Ophthalmology, Emory University School of Medicine, Atlanta, Ga (Drs Martin and Grossniklaus); Department of Ophthalmology, University of Kentucky, Lexington (Drs Cordahi and Schmeisser); and New England Eye Center, Boston, Mass (Dr Ashton).; Dr Pearson is now with the Department of Ophthalmology, University of Kentucky.; Drs Pearson and Ashton have applied for a patent on the cyclosporine sustained-release device and as such may have a financial interest in it.

Arch Ophthalmol. 1996;114(3):311-317. doi:10.1001/archopht.1996.01100130307014

Objectives:  To examine the clearance of cyclosporine after intravitreal injection and to assess the kinetics and toxic effects of an intravitreal device that provides sustained delivery of cyclosporine.

Methods:  Rabbits were divided into two groups to evaluate (1) the elimination kinetics after 1-μg and 10-μg intravitreal injections of cyclosporine and (2) the levels produced after implantation of a device that contained cyclosporine over 6 months. The toxic effects of the intravitreal device over 6 months were assessed in rabbits and cynomolgus monkeys.

Results:  After the 10-μg injection, the half-life was longer (10.8 hours vs 4.2 hours) and the distribution volume was smaller (1.7 mL vs 3.2 mL) than after the 1-μg injection. This difference can be attributed to saturable partitioning of the drug. The device resulted in a vitreous concentration of approximately 500 ng/mL throughout the study period. In the rabbit it resulted in reversible lens opacification and decreased b-wave amplitude. This toxic effect was not detected in the monkey.

Conclusions:  The device produces sustained intravitreal levels of cyclosporine. Although it was associated with reversible toxic effects in the rabbit, it was well tolerated in primates. Sustained-release implants are a promising new treatment for chronic uveitis.

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