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Abstract #27958 Published in IGR 13-1
Effect of SPP 301, an endothelin antagonist, on intraocular pressure in glaucomatous monkey eyes
Wang R-F; Podos SM; Serle JB; Baltatu OCCurrent Eye Research 2011; 36: 41-46
Purpose: To evaluate the effect of topical application of avosentan (SPP 301), endothelin receptor type A antagonist, on intraocular pressure (IOP) in monkey eyes with laser-induced unilateral glaucoma. Materials and Methods: A multiple-dose study was performed in eight glaucomatous monkey eyes that were topically treated with SPP 301 by applying a 50 l drop (25 lnull2) at 9:30 a.m. and 3:30 p.m. for 5 consecutive days at three concentrations (0.003%, 0.03%, or 0.3%). IOP was measured hourly for 6 hrs on each day of the study beginning at 9:30 a.m. for one baseline day, one vehicle-treated day, and treatment days 1, 3, and 5. Results: Twice daily administration of each of the three concentrations of SPP 301 for 5 days significantly (p<0.05) reduced IOP. The maximum reduction in IOP occurred 2 or 3hrs after morning dosing and was 1.8 (plus or minus) 0.8 (mean (plus or minus) SEM) mmHg (6%) for 0.003% SPP 301, 4.1 (plus or minus) 0.7 mmHg (13%) for 0.03% SPP 301, and 7.1 (plus or minus) 1.3 mmHg (21%) for 0.3% SPP 301. The longest duration of IOP reduction was for 2hrs with 0.003% SPP 301, and was for at least 6hrs with 0.03% and 0.3% concentrations. Compared to 0.03% or 0.003% concentrations, 0.3% SPP 301 produced a greater (p<0.05) IOP reduction. IOP was reduced in fellow untreated normal eyes 2hr after morning dosing with 0.3% SPP 301, maximum reduction in IOP (11%) occurred on day 1. Of the eyes treated with 0.3% SPP 301, one eye demonstrated mild conjunctival discharge and one eye was closed for 5min after dosing. Conclusion: Topically applied SPP 301, an endothelin antagonist, reduced IOP in glaucomatous monkey eyes in a dose-dependent manner. Endothelin antagonists, a novel class of compound, may have potential for the treatment of glaucoma.
R.-F. Wang. Department of Ophthalmology, Mount Sinai School of Medicine, Box 1183, One Gustave L. Levy Place, New York, NY 10029, United States. rong-fang.wang@mssm.edu
Classification:
5.2 Primates (Part of: 5 Experimental glaucoma; animal models)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)