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F. J. Lopez, A. Shafiee, S. C. Uhrinek, K. W. Ward; BOL-303242-X, A Non-Steroidal Selective Glucocorticoid (GC) Receptor Agonist (SEGRA), Exhibits Pronounced Efficacy in the Rabbit Atropine-Induced Dry Eye Model. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3662.
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BOL-303242-X is a Selective Glucocorticoid Receptor Agonist (SEGRA) currently of interest for the treatment of a variety of ocular diseases. SEGRAs may offer an improved clinical safety profile compared to steroidal glucocorticoids (GCs). GCs, routinely used in ophthalmology for their potent anti-inflammatory properties, exhibit side effects that limit their therapeutic use. In the eye, GC treatment has been associated with cataracts, elevation of intraocular pressure (IOP) and potentially glaucoma. In these studies, we evaluated the efficacy of BOL-303242-X and compared to that of dexamethasone in the rabbit atropine-induced dry eye model.
A dry eye syndrome was induced in female rabbits by administering atropine three times a day. Dexamethasone and BOL-303242-X were dosed topically after atropine administration. Tear volume (TV) using the Schirmer test, tear breakup time (TBUT) and corneal staining (CS) were measured.
In the first experiment, 0.1% and 0.3% BOL-303242-X prevented atropine-induced dry eye syndrome. Vehicle-treated animals showed statistically significant reductions versus baseline in TV and TBUT at 1, 3 and 7 days after atropine administration. Both doses of BOL-303242-X showed statistically significant improvements in TV and TBUT when compared to the vehicle-treated groups. In the second study, reductions in TV and TBUT at 1, 3, 6 and 8 days versus baseline were observed in vehicle-treated. BOL-303242-X significantly blocked atropine-induced dry eye at all time points for both TV and TBUT. Dexamethasone significantly blocked the atropine effect on TBUT at 1, 3, 6 and 8 days; whereas, for TV significant differences were only seen at 3, 6 and 8 days compared to vehicle-treated animals. CS was not altered in either experiment.
These data indicate that overall BOL-303242-X, a SEGRA, has equivalent efficacy as dexamethasone in a model of dry eye in the rabbit. Because of the selective properties of BOL-303242-X, the compound may offer a better therapeutic index for conditions that may require chronic ocular treatment with GCs.
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