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Kazumi Moriyuki, Yoshikazu Goto, Shinsaku Yamane, Yasuo Ochi, Yasushi Hirota; IOP-lowering effect and ocular safety of ONO-0476, a novel prodrug of prostanoid EP2 receptor agonist, in normotensive cynomolgus monkeys. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5711.
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© ARVO (1962-2015); The Authors (2016-present)
ONO-0476 (ONO Pharmaceutical Co., Ltd., Osaka Japan) is a novel prodrug of prostanoid EP2 receptor agonist. The purpose of this study was to evaluate the IOP-lowering effect and the ocular safety of ONO-0476 in normotensive cynomolgus monkeys.
IOP-lowering effects of ONO-0476 (0.03-3 μg/mL) and latanoprost (50 μg/mL) were evaluated in male cynomolgus monkeys. Drops were administered topically in a 30 μL volume once into each eye for 7 days. IOP was evaluated by using an applanation pneumatonometer just before and at 4, 8, 12, and 24 hours after ocular administration on days 1 and 7 as well as at 48 and 72 hours after the last administration. Ocular safety was evaluated by using portable slit lamp, laser flare photometry, and ultrasound pachymetry in a 4-week repeated dosing study in male cynomolgus monkeys.
ONO-0476 (0.03-3 μg/mL) caused IOP reduction in a dose-dependent manner. The IOP reduction of ONO-0476 at 0.1μg/mL (maximal reduction of IOP: 5.6±0.5 mmHg, on day 7) was comparable to that of latanoprost (maximal reduction of IOP: 4.9±0.4 mmHg, on day 7). For, higher doses of ONO-0476, it caused more potent IOP reduction (maximal reduction of IOP: 7.7±0.5 mmHg, 11.0±0.8 mmHg, and 13.1±1.1 mmHg at 0.3, 1, and 3 μg/mL, respectively, on day 7) than latanoprost. During 4-week repeated dosing of ONO-0476 at 1 μg/mL, there were no evidence of significant toxicity.
ONO-0476 causes potent and sustained IOP reduction, and has good tolerability following topical dosing. ONO-0476 is an attractive candidate for treatment of glaucoma and ocular hypertension.
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