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Tomohiro Karakawa, Shinsaku Yamane, Kazufumi Nagai, Shintaro Nakao, Tsutomu Shiroya, Yutaka Shichino; Effect of ONO-9054 on Aqueous Humor Dynamics in Monkeys. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1998.
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© ARVO (1962-2015); The Authors (2016-present)
ONO-9054 (Ono Pharmaceuticals, Osaka Japan) is a novel prodrug compound. ONO-9054 is an isopropyl ester derivative of the free acid ONO AG-367 that has been classified as a dual FP/EP3 agonist that may be effective in lowering intraocular pressure in humans. The purpose of this study was to investigate the effect of ONO-9054 on the aqueous humor dynamics in cynomolgus monkeys.
Aqueous humor flow was measured with a fluorophotometer in monkeys. Ophthalmic vehicle, timolol (5000 μg/mL), latanoprost (50 μg/mL) and ONO-9054 (3 μg/mL) were administered topically into the eye, and aqueous humor flow rate and intraocular pressure (IOP) measurements were conducted. Outflow facility was measured by a two-level, constant-pressure perfusion method in monkeys. Latanoprost (50 μg/mL) and ONO-9054 (3 and 30 μg/mL) were administered to the eye unilaterally, and the contralateral eye was administered ophthalmic vehicle solution. Measurements of outflow facility and IOP were conducted.
Timolol, latanoprost, and ONO-9054 reduced IOP. Timolol decreased the aqueous humor flow (0.93 ± 0.16 μL/min) relative to vehicle (1.88 ± 0.13 μL/min). On the other hand, ONO-9054 at 3 μg/mL (2.06 ± 0.24 μL/min) and latanoprost (2.05 ± 0.08 μL/min) had no effect on aqueous humor flow. When compared with the contralateral vehicle-treated eyes (0.62 ± 0.10 μL/min/mmHg), latanoprost had no effect on the outflow facility (0.62 ± 0.11 μL/min/mmHg). Likewise, ONO-9054 at 3 μg/mL had no effect on the outflow facility (0.56 ± 0.08 μL/min/mmHg). On the other hand, ONO-9054 at 30 μg/mL slightly increased outflow facility (0.87 ± 0.09 μL/min/mmHg) relative to contralateral eyes (0.66 ± 0.08 μL/min/mmHg).
ONO-9054, a dual agonist for prostaglandin FP and EP3 receptors, did not have any effect on aqueous humor flow. The present results suggest that the mechanism of IOP-lowing for ONO-9054 appears to involve an enhancement of uveoscleral outflow, similar to the mechanism reported for pure FP receptor agonists, and an effect on conventional outflow pathways.
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