title: Effect of SPP 301, an endothelin antagonist, on intraocular pressure in glaucomatous monkey eyes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  A multiple-dose study was performed in eight glaucomatous monkey eyes that were topically treated with SPP 301 by applying a 50 µl drop (25 µl × 2) 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 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. IOP was reduced in fellow untreated normal eyes 2 hr 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 5 min after dosing.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Ophthalmology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA. rong-fang.wang@mssm.edu
authors.forename: Rong-Fang
authors.initials: RF
authors.lastname: Wang
authors.forename: Steven M
authors.initials: SM
authors.lastname: Podos
authors.forename: Janet B
authors.initials: JB
authors.lastname: Serle
authors.forename: Ovidiu C
authors.initials: OC
authors.lastname: Baltatu
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D005260:Female; D005901:Glaucoma / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects*; D008252:Macaca fascicularis; D011725:Pyridines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D014065:Tonometry, Ocular
chemical_list: D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D011743:Pyrimidines; C484919:Avosentan