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G Zhan, CB Toris, CB Camras, MA McLaughlin; The Mechanism by Which Brinzolamide Reduces Intraocular Pressure in Monkeys and Rabbits . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3277.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the mechanism by which brinzolamide, a topical carbonic anhydrase inhibitor, reduces intraocular pressure (IOP) in hypertensive cynomolgus monkey eyes and in normotensive Dutch-belted rabbit eyes. Methods: One eye each of 12 monkeys was treated with laser burns to the trabecular meshwork to elevate IOP. At least two months later, under ketamine sedation, IOP was measured by pneumatonometry, and aqueous flow and outflow facility were determined by a fluorophotometric method. Uveoscleral outflow was calculated. Several weeks later, both eyes were treated with brinzolamide 1% at 5:00 p.m. the evening before and at 8:00 a.m. and 12:00 noon on the measurement day. All measurements were repeated as before. One eye each of 12 rabbits was treated with brinzolamide as above. The fellow eye received vehicle. Without anesthesia, IOP was measured by pneumatonometry and aqueous flow by fluorophotometry (n=12). With anesthesia, outflow facility (n=6) and uveoscleral outflow (n=6) were determined by invasive methods. Two-tailed, paired t-tests were used to determine statistical significance. Results: Two hours after brinzolamide treatment to hypertensive monkey eyes compared to baseline, IOP decreased from 32.2±12.0 (mean ± SD) to 24.9±7.8 mmHg (p=0.01), and aqueous flow decreased from 2.1±1.1 to 1.4±0.5 µl/min (p=0.05). Four hours after brinzolamide treatment to rabbit eyes, IOP was 21.3±2.1 and 23.8±1.9 mmHg (p=0.001) and aqueous flow was 2.2±0.5 and 2.7±0.6 µl/min (p=0.02) in treated and contralateral vehicle-treated control eyes, respectively. No other parameters were significantly altered by treatment. Conclusion: Brinzolamide reduced IOP in normotensive rabbit eyes and hypertensive monkey eyes predominantly by reducing aqueous flow with no effect on aqueous drainage. Both species respond to brinzolamide in a manner similar to humans making them useful models to study carbonic anhydrase inhibitors and aqueous humor dynamics.
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