Abstract
Purpose: :
To evaluate the effect of topical application of SPP 635, a renin inhibitor, on intraocular pressure (IOP) in monkey eyes with laser-induced unilateral glaucoma.
Methods: :
A multiple-dose study was performed in 8 glaucomatous monkey eyes with 3 concentrations of SPP 635, 0.2%, 0.3% and 0.4%. IOP was measured hourly for 6 hrs on each day of the study beginning at 9:30 a.m. Following one baseline day (untreated) and one vehicle-treated day (50µl drop of vehicle to the glaucomatous eye at 9:30 a.m.), a 50µl drop (25µl x 2) of SPP 635, 0.2%, 0.3% or 0.4%, was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days.
Results: :
Twice daily administration of each of the 3 concentrations of SPP 635 for 5 days significantly (p<0.05) reduced IOP in groups of 8 glaucomatous monkey eyes. The maximum reduction in IOP occurred 3 or 4 hrs after morning dosing and was 4.3 ± 0.8 (mean ± SEM) mmHg (14%) for 0.2% SPP 635, 5.3 ± 1.0 mmHg (19%) for 0.3% SPP 635, and 8.0 ± 1.3 mmHg (25%) for 0.4% SPP 635. The longest duration of IOP reduction was for 6 hrs with 0.2% or 0.3% SPP 635, and was for at least 18 hrs with 0.4% concentration. Compared to 0.2% or 0.3% concentrations, 0.4% SPP 635 produced a greater (p<0.05) IOP reduction and longer duration of IOP reduction (18 vs. 6 hrs). Mild conjunctival discharge appeared in 2 of 8 eyes, and hyperemia appeared in 2 eyes with the 0.3% and 0.4% concentrations on treatment days 3 and 5.
Conclusions: :
Topically applied SPP 635, a new renin inhibitor, reduces IOP in glaucomatous monkey eyes in a dose-dependent manner. Renin inhibitors, a novel class of compounds, may have potential for the treatment of glaucoma.
Keywords: intraocular pressure