Distribution of cyclosporine a in ocular tissues after topical administration of cyclosporine a cationic emulsions to pigmented rabbits

摘要

PURPOSE: The aim of this study was to compare the ocular and systemic distribution of cyclosporine A (CsA) in rabbits after the instillation of preservative-free CsA cationic and anionic emulsions. METHODS: For the single-dose pharmacokinetic (PK) study, rabbits were instilled with 50 ??L of the test material. For the multiple-dose PK study, rabbits were instilled twice daily with Restasis or once daily with NOVA22007 for 10 days. At each time point, the cornea, conjunctiva, and whole blood were harvested for CsA quantification. Ocular and systemic distribution were determined after 4 times daily instillations with 50 ??L of H-CsA cationic and anionic emulsions for 7 days. Restasis was used as a reference in all studies. RESULTS: Single-dose PK data demonstrated that NOVA22007 0.1% and 0.05% delivered higher CsA concentrations to the cornea than Restasis [concentration maximum (Cmax): 2692, 1372, and 748 ng/g, respectively] and have a better exposition (area under the curve). Conjunctival Cmax values were 1914, 696, and 849 ng/g and area under the curve values were 3984, 2796, and 2515 ng/g??h, for either dose of the cationic emulsions and Restasis, respectively. The multiple-dose PK and the H-CsA distribution data demonstrated that the systemic distribution after repeated instillations was low and comparable for all emulsions. CONCLUSIONS: These data demonstrate that the CsA cationic emulsions were more effective than Restasis at delivering CsA to target tissues, thus confirming the potential advantage of cationic emulsions over anionic emulsions as vehicle for ocular drug delivery for the treatment of ocular surface diseases.