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Frederic Lallemand, Grégory Lambert, Laura Rabinovich, Philippe Daull, Jean-Sébastien Garrigue; Distribution of Cyclosporine A in Ocular Tissues After Topical Administration of Cyclosporine A-Cationic Emulsion to Pigmented Rabbits. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3785.
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© ARVO (1962-2015); The Authors (2016-present)
The goal of the present studies was to compare the ocular and systemic cyclosporine A (CsA) distribution following single and multiple dosing in pigmented rabbits of the CsA-cationic emulsion and Restasis®.
Cationic oil-in-water emulsions containing various concentrations of CsA, ranging from 0.025 to 0.1% were applied in the conjunctival sac of pigmented rabbits, as a single instillation for single dose PK, or in a repeated manner for multiple doses PKs. For the single dose PK, 6 animals per time point were instilled once with 50 µl of the test material. At each time point (0.33, 0.67, 1, 2, 4, 8, 12, 24, 48, and 72h) the cornea, conjunctiva and whole blood were harvested for CsA concentration determination. For the multiple dose PKs, the rabbits were instilled with 50µl, either qid for 7 days, or bid for 10 days, before collecting either, eyes and general organs, or the cornea, conjunctiva and whole blood, respectively. Restasis® was used as a reference in the 3 studies.
Single dose PK data demonstrated that the cationic emulsion was more effective than Restasis® at delivering CsA to the cornea (Cmax: 1372 vs 748 ng/g; AUC: 26477 vs. 14210 ng/g.h, respectively). Conjunctival concentrations were not statistically different; Cmax: 696 vs. 849 ng/g, AUC: 2781 vs. 2375 ng/g.h, for CsA-cationic emulsion and Restasis®, respectively. The multiple dose PKs confirmed that there was no systemic absorption, with values below the LOD (0.1 ng/ml) for the CsA-cationic emulsion. The use of 3H-CsA demonstrated that the systemic distribution following repeated instillations was indeed low for both CsA-cationic emulsion and Restasis®, and comparable.
The data demonstrated that the CsA-cationic emulsion was more effective than Restasis® at delivering therapeutic doses of CsA to target tissues, thus confirming the advantage of cationic emulsions over anionic emulsions as vehicle for ocular delivery.
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