Evaluation of a delivery system providing long-term release of cyclosporine.

Journal Article (Journal Article)

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-microgram and 10-microgram 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-microgram 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-microgram 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.

Full Text

Duke Authors

Cited Authors

  • Pearson, PA; Jaffe, GJ; Martin, DF; Cordahi, GJ; Grossniklaus, H; Schmeisser, ET; Ashton, P

Published Date

  • March 1996

Published In

Volume / Issue

  • 114 / 3

Start / End Page

  • 311 - 317

PubMed ID

  • 8600892

International Standard Serial Number (ISSN)

  • 0003-9950

Digital Object Identifier (DOI)

  • 10.1001/archopht.1996.01100130307014


  • eng

Conference Location

  • United States