Distribution of cyclosporin A in ocular tissues after topical administration to albino rabbits and beagle dogs

• Published in: Current eye research 1999, Vol.18 (2), p.91-103
• Main Authors: Acheampong, Andrew A., Shackleton, Martha, Tang-Liu, Diane D.-S., Ding, Shulin, Stern, Mike E., Decker, Robert
• Format: Article
• Language: English
• Subjects: Absorption; Administration, Topical; Animals; Ciliary Body - metabolism; Conjunctiva - metabolism; Cornea - metabolism; Cyclosporine - administration & dosage; Cyclosporine - pharmacokinetics; Dogs; Dose-Response Relationship, Drug; Emulsions; Eye - metabolism; Female; Iris - metabolism; Lacrimal Apparatus - metabolism; Lens, Crystalline - metabolism; Male; Ophthalmic Solutions - administration & dosage; Ophthalmic Solutions - pharmacokinetics; Rabbits; Sclera - metabolism; Tissue Distribution
• ISSN: 0271-3683; 1460-2202
• DOI: 10.1076/ceyr.18.2.91.5381

Purpose. To determine the ocular pharmacokinetics of cyclosporin A after topical ophthalmic administration. Methods. Radiolabled cyclosporin A in either a castor oil-in-water emulsion or a corn oil ointment was applied to the eyes of beagle dogs or albino rabbits using the following paradigms: (i) single doses of 0.2% emulsion to rabbits and dogs, (ii) single doses of 0.05%, 0.2%, or 0.4% emulsion to rabbits, (iii) multiple doses of 0.2% emulsion to dogs, (iv) single and multiple doses of 0.2% ointment to rabbits. The distribution of cyclosporin A was determined by measuring the distribution of radio-activity. Results. After a single dose, cyclosporin A was rapidly absorbed into the conjunctiva (C max : dogs, 1490 ng/g; rabbits, 1340 ng/g) and cornea (C max : dogs, 311 ng/g; rabbits, 955 ng/g). High concentrations (>300 ng/g) could be detected in the cornea up to 96 hours post-dose. Lower concentrations were found in the intraocular tissues, and systemic absorption was minimal. After multiple doses, there was some accumulation in the cornea, lens, lacrimal gland, and iris-cilliary body, but limited accumulation in the conjunctiva and sclera. Ocular tissue concentrations of cyclosporin A increased with increasing dose concentration; proportionally in lacrimal gland and intraocular tissues; less than proportionally in conjunctiva and cornea. The pharmacokinetic profile of the cyclosporin A corn oil ointment was similar to that of the emulsion. Conclusions. Topical ophthalmic cyclosporin A penetrated into extraocular tissues at concentrations adequate for local immunomodulation while penetration into intraocular tissues was much less and absorption into the blood was minimal.