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Abstract: BOL-303242-X

In Vivo Ocular Efficacy Profile of BOL-303242-X, a Novel Selective Glucocorticoid Receptor Agonist, In Rabbit Models of Ocular Disease.
Invest Ophthalmol Vis Sci. 2010 Sep 29. [Epub ahead of print]
Shafiee A, Bucolo C, Budzynski E, Ward KW, Lopez FJ.
Preclinical Pharmacology, Bausch & Lomb, Rochester, United States.

Purpose: To compare BOL-303242-X (formerly ZK-245186) efficacy, a novel Selective Glucocorticoid Receptor Agonist (SEGRA), to dexamethasone (DEX) in rabbit models of ocular disease. The effects of topical BOL-303242-X and DEX on intraocular pressure (IOP) and body weight changes were also evaluated.

Methods: Dry eye was induced by atropine sulfate administration, followed by treatment with saline, BOL-303242-X (0.1-1.0%), DEX (0.1%), Restasis® 0.05%, or Refresh Endura for 7-8 days. For paracentesis studies, vehicle, BOL-303242-X (0.1%, 0.5%, and 1.0%), or DEX (0.1%) were repeatedly administered topically 3 hours before paracentesis and continued for 90 min afterwards. For IOP and body weight measurements, right eyes of rabbits were topically treated with vehicle, BOL-303242-X (1.0% or 0.1%) or DEX (0.1%) four times per day for 6 weeks.

Results: In the dry eye model, BOL-303242-X and DEX were fully efficacious, maintaining tear volume and tear breakup time (TBUT) at baseline levels. Although Restasis improved tear volume versus vehicle, no changes were observed in TBUT. In the paracentesis study, BOL-303242-X and DEX improved ocular inflammation. BOL-303242-X reduced protein and PGE2 levels. Finally, BOL-303242-X showed no effects on integrated IOP or body weight, while DEX significantly increased integrated IOP and prevented the increase of body weight observed in the vehicle-treated animals.

Conclusions: BOL-303242-X shows full anti-inflammatory efficacy (similar to DEX) in experimental models of dry eye and post-operative inflammation, while demonstrating reduced effects in IOP and body weight. These data indicate that BOL-303242-X, a SEGRA, shows efficacy similar to traditional steroids, while exhibiting an improved side effect profile in IOP/muscle wasting.