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R.–F. Wang, D.J. Gagliuso, T.W. Mittag, S.M. Podos, R. Ueno, T. Habe; Effect Of RUG–015 On Aqueous Humor Dynamics In Monkeys . Invest. Ophthalmol. Vis. Sci. 2004;45(13):2094.
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Purpose: To evaluate the effects of RUG–015, a prostanoid, on intraocular pressure (IOP) in glaucomatous monkeys in 3 concentrations (0.0001%, 0.001%, and 0.01%) as compared to 0.005% latanoprost, and on aqueous humor dynamics in normal monkeys. Methods: A multiple–dose study was performed in 8 monkeys with unilateral laser–induced glaucoma. One 30µl drop of RUG–015 (0.0001%, 0.001%, or 0.01%) or latanoprost was topically applied to the glaucomatous eye at 9:30 a.m. for 5 consecutive days. IOP was measured hourly for 6 hrs beginning at 9:30 a.m. for one baseline day, one vehicle–treated day, and treatment days 1,3, and 5. Tonographic outflow facility (C) and fluorophotometric flow rates of aqueous humor (F) were measured in 9 normal monkeys before and after a single dose of 0.005% RUG–015. Results: Once daily administration of all 3 concentrations of RUG–015 or latanoprost for 5 days all significantly (p<0.05) reduced IOP in groups of 8 glaucomatous monkey eyes. The maximum reduction of IOP occurred 2 hrs after each morning dosing and was 3.0 ± 0.3 (mean ± SEM) mmHg (9%) for 0.0001% RUG–015, 7.6 ± 0.6 mmHg (23%) for 0.001% RUG–015, 6.3 ± 0.4 mmHg (18%) for 0.01% RUG–015, and 6.6 ± 0.6 mmHg (20%) for 0.005% latanoprost. Enhancement of the ocular hypotensive effect was observed with repeated dosing for all 3 concentrations of RUG–015 and with latanoprost. The 0.001% RUG–015 produced a greater magnitude (23% vs. 9%; p<0.005) and longer duration (24 hrs vs. 4 hrs) of IOP reduction than 0.0001% RUG–015. RUG–015 at 0.01% did not produce further reduction of IOP than the 0.001% concentration. Compared to 0.005% latanoprost, 0.001% RUG–015 caused a greater reduction of IOP (p<0.05) at some time–point measurements during the 5 days of treatment. Compared with either vehicle–treated control eyes or baseline values, C and F were not altered (p>0.80) after a single dose of 0.005% RUG–015 in 9 normal monkeys. Conclusions: RUG–015 reduces IOP in a dose–dependent manner in glaucomatous monkey eyes. The reduction of IOP produced by 0.001%RUG–015 is comparable or better than that obtained with 0.005% latanoprost. RUG–015 appears to reduce IOP by enhancing uveoscleral outflow.
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