Pharmacokinetic and toxicity study of an intraocular cyclosporine DDS in the anterior segment of rabbit eyes.
OBJECTIVE
To establish the safety and pharmacokinetic efficacy of an Oculex Drug Delivery System (DDS; Oculex Pharmaceuticals, Inc., Sunnyvale, CA) containing cyclosporin A (CsA) in the anterior segment of the rabbit eye.


METHODS
The Oculex DDS is an intraocular, sustained-release, drug delivery system comprising a biodegradable lactic acid-glycolic acid copolymer. A controlled prospective study was performed that involved implanting a DDS containing 0.5 mg of CsA into the anterior chamber (AC) of the right eyes of 16 New Zealand White rabbits. A placebo DDS was implanted into the left eyes of these same rabbits as the control. Slit lamp examinations and AC taps were performed serially, and the rabbits were killed and the globes removed at 2, 4, 8, and 12 weeks for histology and determination of CsA drug levels. Analysis of CsA levels was performed with high-performance liquid chromatography-mass spectrometry.


RESULTS
High concentrations of CsA were detectable in all layers of the cornea (epithelium, corneal stroma and endothelium) throughout the 3-month period. Low CsA levels were detected in the aqueous, whereas no CsA was detectable in the blood. There were no adverse reactions observed.


CONCLUSIONS
The Oculex DDS CsA device is effective in delivering long-term levels of CsA to corneal tissues, without adverse effects. Further studies in an animal model of corneal transplant rejection should be performed to determine the potential of this device in the prophylaxis and treatment of corneal transplant rejection in humans.
Singapore Eye Research Institute, Singapore.
Julian T S
JT
Theng
Seng-Ei
SE
Ti
Lei
L
Zhou
Kwok-Wai
KW
Lam
Soon Phaik
SP
Chee
Donald
D
Tan
Seng Ei
SE
Ti
D020341:Absorbable Implants; D000818:Animals; D000869:Anterior Eye Segment / Q000187:drug effects / Q000378:metabolism*; D001082:Aqueous Humor / Q000378:metabolism; D001672:Biocompatible Materials; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000633:toxicity*; D016503:Drug Delivery Systems; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics* / Q000633:toxicity*; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011446:Prospective Studies; D011817:Rabbits; D012449:Safety
D001672:Biocompatible Materials; D007166:Immunosuppressive Agents; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine