Enalaprilat and enalapril maleate eyedrops lower intraocular pressure in rabbits.
OBJECTIVE
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-beta-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.
University of Iceland, Reykjavik, Iceland. thorstlo@hi.is <thorstlo@hi.is>
Thorsteinn
T
Loftsson
Sigridur
S
Thorisdóttir
Hafrun
H
Fridriksdóttir
Einar
E
Stefánsson
D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry; D004656:Enalapril / Q000008:administration & dosage* / Q000737:chemistry; D015773:Enalaprilat / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000737:chemistry; D011817:Rabbits; D013997:Time Factors; D013999:Timolol / Q000008:administration & dosage; D014065:Tonometry, Ocular
D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D004656:Enalapril; D013999:Timolol; D015773:Enalaprilat