Comparison the Pharmacokinetics and Pharmacodynamics of Cyclosporine A Ophthalmic Gel and Cyclosporine A Ophthalmic Emulsion in New Zealand White Rabbits

Abstract

Objective: Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and is accompanied by ocular symptoms. We aimed to compare the pharmacokinetics and pharmacodynamics of Cyclosporine A after a single administration in rabbits with 0.05% Cyclosporine A Ophthalmic Gel or 0.05% Restasis Ophthalmic Emulsion (control group). Methods: A total of 162 rabbits were randomly divided into Cyclosporine A (0.05%) Ophthalmic Gel (CsA gel) group or cyclosporine A (0.05%) ophthalmic emulsion (Restasis Ophthalmic Emulsion) group. Pharmacokinetic and pharmacodynamics studies were performed. Results: CsA gel administration resulted in similar T_max and increased CsA concentration and concentration (C_max) in tear, conjunctiva, and cornea compared with Restasis after a single dose administrated to the ocular surface. The area under the curve (AUC)_{0–96 h} in the cornea (15,966.17 vs. 2537.92 h*ng/mL, p = 0.000), conjunctiva (9737.22 vs. 3147.99 h*ng/mL, p = 0.000), and tear (5801.12 vs. 3324.62 h*ng/mL, p = 0.042) were significantly higher in CsA gel group than Restasis group. For the pharmacodynamic study, Schirmer tests showed tear secretion was significantly increased after CsA administration with comparable effect in both groups (p > 0.05). Conclusions: CsA gel delivered a higher CsA concentration (C_max) to the rabbit cornea, conjunctiva, and tear, as well as a better exposition AUC compared to Restasis, and demonstrate a comparable pharmacodynamics effect as measured by Schirmer test, no CsA exposure to systemic circulation after administration.