Current eye research · 1999
Distribution of cyclosporin A in ocular tissues after topical administration to albino rabbits and beagle dogs.
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Acheampong A A, Shackleton M, Tang-Liu D D, Ding S, Stern M E, Decker R
Аннотация
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 radioactivity.
RESULTS: After a single dose, cyclosporin A was rapidly absorbed into the conjunctiva (Cmax: dogs, 1490 ng/g; rabbits, 1340 ng/g) and cornea (Cmax: 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.
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 radioactivity.
RESULTS: After a single dose, cyclosporin A was rapidly absorbed into the conjunctiva (Cmax: dogs, 1490 ng/g; rabbits, 1340 ng/g) and cornea (Cmax: 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.