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H. Sakaki, S. Nemoto, T. Kida, T. Tajika, A. Ohtori; Preclinical Toxicity of Difluprednate Emulsion. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2653.
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To evaluate the ocular and systemic safety of difluprednate ophthalmic emulsion, a new strong ocular steroid in development.
Data from 2 preclinical studies in rabbits and dogs will be presented. In the rabbit study, doses of difluprednate ophthalmic emulsion (DFBA) 0.01% and 0.05% were instilled into the eyes of male rabbits (5 per group). In the dog study, 20 beagles received difluprednate ophthalmic emulsion 0.05% and betamethasone sodium (BM) 0.1%. All animals received these doses QID for 4 weeks. Vehicle and saline were instilled into the eyes of the vehicle and negative control group animals, respectively, in the same manner as the test article.
No animals died and no abnormalities were observed in both studies. In the rabbit study, the hematology examination showed a decrease in leukocyte and lymphocyte counts in the DFBA 0.05% group; decreases in ALP, creatinine, C1 and gamma-globulin values and increases in total protein and triglycerides were also noted in this group. Additionally, some animals in DFBA 0.05% group showed high AST, ALT, and total bilirubin values. In the dog study, decreases in lymphocyte and eosinophilic leukocyte counts and their ratios, and an increase in leukocyte ratio were noted in the DFBA 0.05% group. In blood chemistry, increases were noted in LDH, albumin, total cholesterol, Na concentration, and an alpha2-globlin ratio. In the BM 0.1% group, decreases in lymphocyte count and ratio and eosinophilic leukocyte count and ratio, and increase in neutronphilic leukocyte ratio and platelet count were noted. Increases in ALT, albumin, total cholesterol, triglycerides, Na and K concentrations, alpha2-globlin ratio, and decreases in alpha1-globlin ratio and beta-globlin were also found.
These studies suggest no toxicity in the eyes or systemic exposure from treatment with difluprednate ophthalmic emulsion. All changes noted in the test article groups were similar to those of steroids. No vehicle-related toxicity was noted.
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