Abstract
Purpose: :
Topical administration of flunarizine, a non–selective calcium channel blocker, reduces intraocular pressure (IOP) in rabbits, normal and glaucomatous monkeys. The purpose of this study is to determine the mechanism by which flunarizine reduces IOP in normotensive monkey eyes when applied topically.
Methods: :
7 normal monkeys were used in this study. Baseline tonographic outflow facility (C) was measured on day 1. The following day, 50µl drop (25µl x 2) of 0.5% flunarizine was topically applied to one eye of each monkey at 9:30 a.m. and 3:30 p.m.for 3 consecutive days; the fellow control eye received 50µl of vehicle. C measurement was repeated 2 hrs after the morning dose of 0.5% flunarizine on day 4.The same treatment regimen was applied to the measurement of aqueous humor flow rates (F). Baseline F was measured hourly for 4 hours beginning at 9:30 a.m. on day 1.The flow rates were measured at the same time and same period beginning 1 hour after the 5th dose of 0.5% flunarizine on day 4.
Results: :
2 hours after the 5th dose of 0.5% flunarizine to 7 normal monkeys, C (µl /min/mmHg) was increased (p<0.05) by 39% in the drug–treated eyes [1.16 ± 0.20 (mean ± (SEM)] compared to the vehicle–treated control eyes (0.84 ± 0.12) and by 41% compared to the baseline measurement (0.83 ± 0.13). Unilateral topical application of 0.5% flunarizine reduced IOP (p<0.05) bilaterally. The IOP (mmHg) measured tonographically in drug–treated eyes was reduced (p<0.05) by 18% when compared to vehicle–treated control eyes and by 25% when compared to the baseline values. The IOP in fellow control eyes was reduced (p<0.05) by 9% when compared to the baseline values. For 4 hours following the 5th dose of 0.5% flunarizine to 7 monkeys, F (µl /min) was unchanged (p>0.30) when compared to either vehicle–treated control eyes or baseline values.
Conclusions: :
Flunarizine reduces IOP predominantly by increasing tonographic outflow facility in normal monkey eyes.
Keywords: aqueous • intraocular pressure • drug toxicity/drug effects