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Rong-Fang Wang, Donna J. Gagliuso, Thomas W. Mittag, Steven M. Podos; Effect of 15-Keto Latanoprost on Intraocular Pressure and Aqueous Humor Dynamics in Monkey Eyes. Invest. Ophthalmol. Vis. Sci. 2007;48(9):4143-4147. doi: 10.1167/iovs.07-0035.
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purpose. To compare the ocular hypotensive effects of 15-keto latanoprost (KL) with the commercial preparation of latanoprost (Xalatan; Pfizer, New York, NY) in monkey eyes with laser-induced unilateral glaucoma and to evaluate the effects of topical 0.005% KL on aqueous humor dynamics in normal monkey eyes.
methods. Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:30 AM on day 1 (untreated baseline); day 2 (vehicle only); and treatment days 1, 3, and 5 (topical, 30 μL of study drug) in the glaucomatous eyes of four to eight monkeys with unilateral laser-induced glaucoma. KL concentrations of 0.0001%, 0.001%, and 0.01% and latanoprost at 0.005% were studied separately, with a minimum washout period of 2 weeks between studies. Tonographic outflow facility (C) and fluorophotometric aqueous humor flow rates (F) were measured in nine normal monkeys before and after a single topical dose of 0.005% KL in one eye, with a vehicle-only control in the fellow eye.
results. When applied once daily to glaucomatous monkey eyes, all three concentrations of KL and a 0.005% concentration of latanoprost produced significant (P < 0.05) reductions in IOP, with the maximum reduction on treatment day 5, regardless of the drug or concentration studied. The maximum reduction (P < 0.001) from vehicle-only baseline IOP was (mean ± SEM) 3.0 ± 0.3 mm Hg (9%) for 0.0001% KL, 7.6 ± 0.6 mm Hg (23%) for 0.001% KL, 6.3 ± 0.4 mm Hg (18%) for 0.01% KL, and 6.6 ± 0.6 mm Hg (20%) for 0.005% latanoprost. After application of a single dose of 0.005% KL in nine normal monkey eyes, neither C nor F was altered (P > 0.80) when compared with untreated baseline values or vehicle-treated control eyes.
conclusions. The reduction in IOP produced by 0.001% KL was equivalent to, and at some measured time points, greater than the effect produced by 0.005% latanoprost. The IOP reduction by KL in normal monkeys appeared to have no effect on aqueous humor production or tonographic outflow facility and may thus indicate a drug-induced increase in uveoscleral outflow.
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