Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits

. Purpose:  This study aimed to develop low‐viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits. Methods:  Aqueous eyedrops with hydroxypropyl‐β‐cyclodextrin containing 0.01–2.9% (w/v) enalaprilat, 1.0% (w/v) enalapril maleate with cyclodextrin or 0.5% (w/v) timolol were prepared. The eyedrops were administered to rabbits and intraocular pressure (IOP) was measured at various time intervals after the administration and the results (mean of 10 experiments ± standard error of the mean) are expressed as the change from baseline (24.7 ± 3.3 mmHg). Results:  Enalaprilat possessed sufficient stability to be formulated as an aqueous eyedrop solution with a shelf‐life of several years at room temperature. The maximum decline in IOP after topical administration of one drop of 2.9% enalaprilat solution was 6.2 ± 0.7 mmHg at 4 hours after administration. Duration of activity exceeded 10 hours. A 1% enalaprilat solution lowered IOP by 4.4 ± 0.8 mmHg at 4 hours after administration and had similar duration, and was more potent than 0.5% timolol. The enalapril maleate eyedrops resulted in delayed action, showing maximum potency at 10–22 hours after administration and duration of up to 32 hours. Conclusions:  Enalaprilat eyedrops lower IOP in rabbits. The decline in IOP is proportional to the concentration of dissolved enalaprilat in low‐viscosity aqueous eyedrop formulations.