Abstract
Purpose: :
To evaluate the effect of topical application of Avosentan (SPP 301), an endothelin receptor type A antagonist, 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 301, 0.003%, 0.03% and 0.3%. A 50µl drop (25µl x 2) of SPP 301, 0.003%, 0.03%, or 0.3% was topically applied to the glaucomatous eye at 9:30 a.m. and 3:30 p.m. for 5 consecutive days. 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 3 concentrations of SPP 301 for 5 days significantly (p<0.05) reduced IOP in groups of 8 glaucomatous monkeys eyes. The maximum reduction in IOP occurred 2 or 3 hrs after morning dosing and was 1.8 ± 0.8 (mean ± SEM) mmHg (6%) for 0.003% SPP 301, 4.1 ± 0.7 mmHg (13%) for 0.03% SPP 301, and 7.1 ± 1.3 mmHg (21%) for 0.3% SPP 301. The longest duration of IOP reduction was for 2 hrs with 0.003% SPP 301, and was for at least 6 hrs 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. A significant (p<0.05) reduction in IOP at 2 hrs after morning dosing, up to 2.0 ± 0.5mmHg (11%), was also seen in fellow untreated normal eyes with the 0.3% SPP 301. Mild conjuctival discharge appeared in one of 8 eyes, and a closed eye after dosing appeared in 1 of 8 eyes with the highest concentration of 0.3%.
Keywords: intraocular pressure