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Abstract #48812 Published in IGR 14-1
Effect of SPP 635, a renin inhibitor, on intraocular pressure in glaucomatous monkey eyes
Wang RF; Podos SM; Serle JB; Baltatu OCExperimental Eye Research 2012; 94: 146-149
The effect of topical application of SPP 635, a renin inhibitor, on intraocular pressure (IOP) was evaluated in the eyes of monkeys with laser induced unilateral glaucoma. 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 h on each day of the study beginning at 9:30 a.m. Following one baseline day (untreated) and one vehicle-treated day (50 μl drop of vehicle to the glaucomatous eye at 9:30 a.m.), a 50 μl drop (25 μl × 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. Twice daily administration of each of the 3 concentrations of SPP 635 for 5 days significantly (p < 0.05) reduced IOP. The maximum reduction in IOP occurred 3 or 4 h 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 h with 0.2% or 0.3% SPP 635, and was for at least 18 h with 0.4% concentration. Compared to 0.2% or 0.3% concentrations, 0.4% SPP 635 produced a greater (p < 0.05) and longer duration of IOP reduction (18 vs. 6 h). 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. Topically applied SPP 635, a new renin inhibitor, reduces IOP in glaucomatous monkeys in a dose-dependent manner. Renin inhibitors, are a novel class of compounds which may have potential for the treatment of glaucoma.
Department of Ophthalmology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, USA. Rong-fang.wang@mssm.edu
Full articleClassification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
5.2 Primates (Part of: 5 Experimental glaucoma; animal models)