Effect of CS-088, an angiotensin AT 1 receptor antagonist, on intraocular pressure in glaucomatous monkey eyes

Abstract

To evaluate the effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure (IOP) in monkey eyes with unilateral laser-induced glaucoma. A multiple-dose study was performed in 8 glaucomatous monkey eyes. One 50 µl drop of CS-088, 2% or 4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. IOP was measured hourly for 6 hours beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and daily for 5 days of treatment with CS-088. The washout period between the two drug concentrations was at least 2 weeks. 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 in IOP began 1 hour after the third dose, and lasted for 3 hours. The maximum reduction in IOP was 5.3± 0.8 (mean±SEM) mmHg (15%) (p<0.001), with the longest duration of IOP reduction of at least 6 hours after dosing on day 5. The 4% dose of CS-088 reduced (p<0.05) IOP from 1 to 5 hours after the first dose. The maximum reduction in IOP was 6.9±1.0 mmHg (20%), with the longest duration of IOP reduction of at least 18 hours 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%. Topically applied CS-088, a new antagonist drug at the angiotensin AT1 receptor, reduced IOP in glaucomatous monkey eyes in a dose-dependent manner.