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Rong-Fang Wang, Janet B. Serle, Casey Kopczynski; Effect of 0.04% AR-13324 on Aqueous Humor Dynamics in Normotensive Monkey Eyes. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1994.
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Topical administration of selective inhibitors of rho kinase (Rock) has been shown to reduce intraocular pressure (IOP) in rabbits, monkeys, healthy human eyes and patients with ocular hypertension and glaucoma. AR-13324 is a Rock inhibitor and an inhibitor of the nor-epinephrine transporter (NET). The purpose of this study is to determine the mechanism by which topically applied AR-13324 reduces IOP in normotensive monkey eyes.
Seven normotensive monkeys were used. Tonographic outflow facility (C) was measured prior to drug administration and repeated 6 hours after administration of 50 µl (25µl × 2) of 0.04% AR-13324 to one eye and an equal volume of vehicle to the contralateral control eye. After a washout period of at least 1 week, baseline aqueous humor flow rates (F) were measured hourly for 6 hours beginning at 10:00 a.m. The following day at 8 a.m., 50 µL (25 µl x 2) of 0.04% AR-13324 was applied to one eye of each animal and vehicle to the fellow eye. Aqueous humor flow rates were measured at the same times as on the baseline day beginning 2 hrs after dosing.
Six hours after a single dose of 0.04% AR-13324 to 7 normal monkey eyes, C was increased (p<0.05) by 53% in drug-treated eyes compared with either contralateral vehicle-treated-control eyes or baseline measurements. The IOP measured by pneumatonometer in treated eyes was reduced (p<0.005) by 25% when compared with baseline measurements and by 24% when compared with contralateral vehicle-treated eyes. For 6 hrs after a single-dose of 0.04% AR-13324, F was reduced (p<0.05) by 20% and 23% when compared with contralateral vehicle-treated eyes and baseline values, respectively.
AR-13324 reduces IOP in normotensive monkey eyes. A dual mechanism of action, increase in tonographic outflow facility and decrease of aqueous humor flow rates, accounts for the IOP reduction in normotensive monkey eyes.
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