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Evaluation of a Delivery System Providing Long-term Release of Cyclosporine
P. Andrew Pearson, MD;
Glenn J. Jaffe, MD;
Daniel F. Martin, MD;
Ghassan J. Cordahi, MD;
Hans Grossniklaus, MD;
Elmar T. Schmeisser, PhD;
Paul Ashton, PhD
Arch Ophthalmol. 1996;114(3):311-317.
Abstract
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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.
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.
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