Effects of a Novel Selective EP2 Receptor Agonist, Omidenepag Isopropyl, on Aqueous Humor Dynamics in Laser-Induced Ocular Hypertensive Monkeys

Abstract

Purpose: To investigate the mechanism of the intraocular pressure (IOP)-lowering effect of a novel selective prostaglandin E2 receptor 2 (EP2) receptor agonist, omidenepag isopropyl (OMDI).

Methods: The effect of OMDI on IOP and aqueous humor dynamics was evaluated in cynomolgus monkeys with unilateral laser-induced ocular hypertension. In a crossover manner, the hypertensive eye of each monkey was dosed once daily with 20 μL of either 0.002% OMDI or vehicle. On day 7 of dosing, IOP was measured by pneumatonometry, aqueous humor flow and outflow facility were evaluated by fluorophotometry, and uveoscleral outflow was calculated mathematically. Treatments were compared by paired t-tests.

Results: OMDI at 0.002% significantly lowered IOP by 27%, 35%, and 44% at 0.5, 1.5, and 4 h after the last dosing, respectively. There was no difference in aqueous humor flow between vehicle and OMDI treatments. When comparing OMDI to the vehicle treatment, outflow facility and uveoscleral outflow were significantly (P < 0.05) increased by 71% and 176%, respectively.

Conclusions: OMDI, a novel IOP-lowering compound, reduced IOP by increasing outflow facility and uveoscleral outflow in nonhuman primates.

Keywords: EP2 receptor; aqueous humor dynamics; glaucoma; intraocular pressure.