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R. Wang, T.W. Mittag, S.M. Podos, T. Yokoyama; Effect of CS-088, an Angiotensin AT1 Receptor Antagonist, on Intraocular Pressure (IOP) in Glaucomatous Monkey Eyes . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4401.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: CS-088, an angiotensin AT1 receptor antagonist, reduces IOP in rabbits. This study evaluates the effect of topical application of 2% and 4 % CS-088 on IOP in monkey eyes with laser-induced unilateral glaucoma. Methods: A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 50µl drop of CS-088, 2% or 4 %, was applied topically to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. IOP was measured hourly for 6 hrs beginning at 9:30 a.m. for one day baseline, one vehicle-treated day, and 5 days of treatment with CS-088. The washout period between tests done on the same animal was at least 2 weeks. Results: Twice daily administration of 2% CS-088 for 5 days did not reduce the IOP until the third dose on day 2 of the treatment regimen. A significant (p<0.02) reduction of IOP occurred beginning 1 hour after the third dose which lasted for 3 hrs. The maximum reduction of IOP was 5.3 ± 0.8 (mean ± SEM) mmHg (15%) (p<0.001), with the longest duration of IOP reduction of at least 6 hrs after dosing on day 5. The 4% dose of CS-088 reduced (p<0.05) IOP from 1 hr to 5 hrs after the first dose. The maximum reduction of IOP was 6.9 ± 1.0 mmHg (20%) (p<0.001), with the longest duration of IOP reduction of at least 18 hrs after administration on day 5. Both 2% and 4 % CS-088 showed enhancement of the ocular hypotensive effect with repeated dosing. 4% CS-088 produced greater (p<0.05) IOP reduction with longer duration of action than 2%. Conclusion: Topically applied CS-088, a new antagonist drug at the angiotensin AT1 receptor, reduced IOP in glaucomatous monkey eyes in a dose- dependent manner.
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