June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Identification of a highly efficacious, ultra-long acting ocular hypotensive agent in non-human primates
Author Affiliations & Notes
  • Carol B Toris
    Ophthalmology, Case Western Reserve University, Cleveland, OH
    Ophthalmology, University of Nebraska Medical Center, Omaha, NE
  • Robert Coleman
    Asterand, Royston, United Kingdom
  • Shan Fan
    Ophthalmology, University of Nebraska Medical Center, Omaha, NE
  • Amanda J Woodrooffe
    Asterand, Royston, United Kingdom
  • David F Woodward
    Allergan, Irvine, CA
  • Footnotes
    Commercial Relationships Carol Toris, Allergan (F), Bausch and Lomb (F), Nicox (F); Robert Coleman, Allergan (F), Asterland (F); Shan Fan, None; Amanda Woodrooffe, Asterand (E); David Woodward, Allergan (E)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4848. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Carol B Toris, Robert Coleman, Shan Fan, Amanda J Woodrooffe, David F Woodward; Identification of a highly efficacious, ultra-long acting ocular hypotensive agent in non-human primates. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4848.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract
 
Purpose
 

In a program to discover drugs that are meaningfully superior to currently available anti-glaucoma drugs in terms of efficacy, potency, and duration of action, the isopropyl ester of a novel structurally non-prostanoid EP2 agonist, PGN9856 (PGN9856-I), was studied in unilateral ocular hypertensive monkeys.

 
Methods
 

Measurements included intraocular pressure (IOP), aqueous flow, fluorophotometric outflow facility, tonographic outflow facility, outflow facility by needle method, central cornea thickness and anterior chamber depth. Uveoscleral outflow was calculated by the Goldmann Equation. Twenty-four hours before measurements commenced animals were dosed once (25ul drop in each eye) with vehicle or drug in a random crossover design. Results with vehicle and drug were compared by two-tailed paired t-tests.

 
Results
 

IOP studies: PGN9856-I reduced IOP in ocular hypertensive eyes over a 0.0001% - 0.01% dose-range. After a single 0.006% dose, the maximal IOP reduction was reached at 48 hours, IOP being reduced to approximately half that of the ocular normotensive contralateral eye. Five days after this dose of PGN 9856-I, the IOP of the treated hypertensive eyes had recovered only to the level of the normotensive controls. The IOP of PGN9856-I treated hypertensive eyes did not return to baseline values until after approximately two weeks. While active, such profound effects in terms of either efficacy or duration of action were not seen with the free acid of this compound, PGN9856. No drug-related side effects were observed. Aqueous humor dynamics study: Compared with vehicle treatment, IOP was reduced at 7, 24 and 26.5 hours after a single dose of 0.0003% PGN9856-I (p<0.0001). Aqueous flow decreased by 20% (p=0.02) and uveoscleral outflow doubled (p<0.03). Outflow facility was not changed when measured three different ways.

 
Conclusions
 

PGN 9856-I is an exceptionally potent, efficacious, and long-acting ocular hypotensive compound. It lowers IOP by a dual mechanism on aqueous humor inflow and uveoscleral outflow.

 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×