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

Arch Ophthalmol. 1996 Mar;114(3):311-7. 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-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Availability
  • Cataract / chemically induced
  • Cataract / physiopathology
  • Cyclosporine / administration & dosage
  • Cyclosporine / pharmacokinetics*
  • Cyclosporine / toxicity
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Drug Evaluation
  • Drug Implants
  • Electroretinography
  • Eye / metabolism
  • Female
  • Half-Life
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / toxicity
  • Injections
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / metabolism
  • Macaca fascicularis
  • Male
  • Rabbits
  • Retina / drug effects
  • Retina / metabolism
  • Retina / physiology
  • Tissue Distribution
  • Vitreous Body / metabolism*


  • Delayed-Action Preparations
  • Drug Implants
  • Immunosuppressive Agents
  • Cyclosporine