Pharmacological and pharmacokinetic study of olmesartan medoxomil in animal diabetic retinopathy models |
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Authors: | Nakamura Hiroaki Inoue Tatsuya Arakawa Naohisa Shimizu Yuki Yoshigae Yasushi Fujimori Izumi Shimakawa Emi Toyoshi Tohru Yokoyama Tomihisa |
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Affiliation: | Pharmacology and Molecular Biology Research Laboratories, Sankyo Co., Ltd., 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan. nakamura_hiroaki@sankyo.co.jp |
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Abstract: | A close relationship between the renin-angiotensin system and the pathophysiology of diabetic retinopathy has been suggested, several angiotensin II type 1 receptor (angiotensin AT1 receptor) antagonists being effective in animal models. Therefore, we examined the efficacy of an angiotensin AT1 receptor antagonist, olmesartan medoxomil (CS-866), in animal retinopathy models. In diabetic stroke-prone spontaneously hypertensive (SHRSP) rats, 4-week treatment with CS-866 prevented the elongation of oscillatory potential peaks dose-dependently which almost normalized at 3 mg/kg/day. Next, in oxygen-induced retinopathy mice, CS-866 at 1 mg/kg significantly prevented the retinal neovascularization. In these animal models, plasma concentrations of CS-866 were comparable to the in vitro IC50 value of the angiotensin AT1 receptor. In summary, our data demonstrated that CS-866 was effective in early and late stage retinopathy models through the inhibition of the angiotensin AT1 receptor. These findings suggest the possibility of CS-866 as a therapeutic agent for diabetic retinopathy. |
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