Abstract
Purpose: :
Topical administration of AR-12286, a selective inhibitor of rho kinase, reduces intraocular pressure (IOP) in rabbits and monkeys. The purpose of this study is to determine the mechanism by which AR-12286 reduces IOP in normotensive monkey eyes when applied topically.
Methods: :
Six normotensive monkeys were used. Tonographic outflow facility (C) was measured prior to drug administration, and repeated 4 hours after administration of 30 µl of 0.6% AR-12286 to one eye and 30 µl vehicle to the contralateral control eye. Baseline aqueous humor flow rates (F) were measured hourly for 4 hours on day 1. The following day, 30 µl of 0.6% AR-12286 was topically applied to one eye, and 30 µl vehicle to the contralateral control eye, one hour before F measurement. F was measured at the same times as on the baseline day beginning 1 hour after dosing. The pupil size was measured with a pupil gauge (mm) under natural room light immediately before drug administration (0 hr), then hourly for 4 hrs after drug administration during the flow measurements.
Results: :
4 hrs after administering a single-dose of 0.6% AR-12286 to 6 normotensive monkey eyes, C was increased (p<0.05) 39% in drug-treated eyes compared to contralateral vehicle-treated eyes. IOP measured tonographically in treated eyes was reduced (p<0.05) 19% when compared with either baseline measurements or contralateral vehicle-treated eyes. For 4 hrs after a single-dose of 0.6% AR-12286, F was unchanged (p>0.60) when compared with either contralateral vehicle-treated eyes or baseline values. The pupil size increased (p<0.05) 5% to13% for at least 4 hrs after drug administration when compared to the baseline values of the same eye. No difference (p>0.30) in pupil size was observed when the drug treated eyes were compared to the vehicle-treated contralateral control eyes.
Keywords: outflow: trabecular meshwork • intraocular pressure