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R.-F. Wang, K. Segal, T. W. Mittag, S. M. Podos; 8-iso Prostaglandins and Aqueous Humor Dynamics in Monkeys - Effect of 17-Phenyl Trinor 8-iso Prostaglandin E2. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4803.
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To evaluate the effects of 17-phenyl trinor 8-iso PGE2 on intraocular pressure (IOP) in monkeys with laser-induced glaucoma, and on aqueous humor dynamics in normal monkeys.
Two single-dose tests were performed on 8 monkeys with unilateral laser-induced glaucoma at concentrations of 0.1% and 0.2%. One 25µl drop of 17-phenyl trinor 8-iso PGE2 was topically applied to the glaucomatous eye at 9:30 a.m. IOP was measured hourly for 6 hrs beginning at 9:30 a.m. Following one baseline day and one vehicle-treated day, a multiple-dose study was carried out in 8 glaucomatous monkey eyes with 0.1% 17-phenyl trinor 8-iso PGE2 applied to the glaucomatous eye at 9:30 a.m. for 5 consecutive days. Tonographic outflow facility (C) and fluorophotometric flow rates (F) were measured in 6 normal monkeys before and after a single dose of 0.2% 17-phenyl trinor 8-iso PGE2 to one eye.
A single dose of either 0.1% or 0.2% 17-phenyl trinor 8-iso PGE2 reduced (p<0.05) IOP for 5 hrs with the maximum reduction of 4.5 ± 0.6 (mean ± SEM) mmHg (15%) in 8 glaucomatous monkeys, and 5.7 ± 1.4 mmHg (19%) in 6 glaucomatous monkeys, respectively. The ocular hypotensive effect was maintained for 5 days with once daily administration of 0.1% 17-phenyl 8-iso PGE2 in 8 glaucomatous monkeys. In 6 normal monkeys, C was increased (p<0.05) by 59% in the drug-treated eyes compared with the vehicle-treated contralateral control eyes and by 69% compared with baseline measurements. F was unchanged (p>0.90).
17-phenyl trinor 8-iso PGE2 reduces IOP in both normal and glaucomatous monkey eyes. An increase in tonographic outflow facility accounts for most if not all of the IOP reduction in normal monkeys. This PG analog appears to lower IOP primarily by increasing trabecular outflow facility.
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