A COMPARTMENTAL MODEL FOR THE OCULAR PHARMACOKINETICS OF CYCLOSPORINEIN RABBITS

Studies were conducted in rabbits to determine the ocular distribution and elimination of cyclosporine, with the objective of developing a c omprehensive pharmacokinetic model. Following a bolus dose into the an terior chamber, drug levels were measured in the aqueous humor, cornea , iris/ciliary body, lens, sclera, and conjunctiva. Cyclosporine was r apidly eliminated from the aqueous, but drug levels in ocular tissues persisted for in excess of 48 hours, particularly in the cornea and ir is/ciliary body. The terminal elimination half life from these tissues was 45 hr and 30 hr, respectively, providing evidence that these tiss ues could act as a reservoir for the drug. It was found that a compart mental model accurately described the experimental data. A single comp artment was used for each of the tissues and fluids sampled, except fo r the cornea, which was subdivided into two compartments, representing its tissue and aqueous regions.