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R.–F. Wang, D.J. Gagliuso, T.W. Mittag, S.M. Podos; Effect of Flunarizine, a Calcium Channel Blocker, on Intraocular Pressure (IOP) in Glaucomatous Monkey Eyes . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3778.
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Purpose: Topical administration of flunarizine, a non selective calcium channel blocker, reduces IOP in rabbits and in normal monkeys. This study evaluates the effect of flunarizine on IOP in single–dose or multiple–dose applications in monkey eyes with unilateral laser–induced glaucoma. Methods: 8 glaucomatous monkeys were used in this study. IOP was measured hourly for 6 hrs on each day of the study. Following one day of baseline IOP measurement, 50µl drop (25µl x 2) was topically applied to the glaucomatous eye with 0.5%, 1% or 2% concentrations. A multiple–dose study was performed with 0.5% flunarizine twice daily for 5 consecutive days. IOP was measured for one baseline day, one vehicle– treated day and treatment days 1,3 and 5. Results: Unilateral topical application of 50µl of 0.5%, 1% or 2% flunarizine to the glaucomatous eye of 8 monkeys reduced IOP (p<0.05) bilaterally. A significant (p<0.01) reduction in IOP occurred for 2 hrs, 3 hrs and 5 hrs, and was up to 2.5 ± 0.5 (mean ± SEM) mmHg (9%), 3.0 ± 0.4 mmHg (10%), and 5.0 ± 0.8 mmHg (18%) in the glaucomatous eyes following doses of the 0.5%, 1% and 2% concentrations, respectively. In the fellow untreated control eyes, a significant (p<0.05) reduction in IOP was observed for 1–2 hrs with the maximum reduction in IOP of 1.3 ± 0.5 mmHg (7%), 1.5 ± 0.3 mmHg (8%) and 2.9 ± 0.7 mmHg (15%) following unilateral application of 0.5%, 1% or 2% flunarizine. The ocular hypotensive effect was enhanced with twice daily administration of 0.5% flunarizine for 5 days. The IOP was significantly (p<0.01) reduced for 2 hrs after the first dose and for at least 6 hrs after the fifth dose. The maximum reduction in IOP was 2.5 ± 0.5 mmHg (9%) on day 1 and 6.0 ± 0.8 mmHg (21%) on day 5 in the treated glaucomatous monkey eyes, and 1.3 ± 0.5 mmHg (7%) on day 1 and 1.5 ± 0.6 mmHg (8%) on day 5 in the untreated contralateral normal eyes. Mild conjunctival discharge appeared in some eyes treated with 0.5% flunarizine. More conjuctival discharge, mild conjuctival hyperemia, eyelid edema and cornea edema appeared in some eyes treated with the 1% and 2% concentrations. Conclusions: Flunarizine reduces IOP in a dose–dependent manner when administered to glaucomatous monkey eyes, but also has some effect on the contralateral, untreated eyes.
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