April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
BOL-303242-X, a Selective Glucocorticoid Receptor Agonist (SEGRA), Offers a Better in vivo Side Effect Profile Than Dexamethasone on Intraocular Pressure Elevation in Normotensive Rabbits
Author Affiliations & Notes
  • E. Budzynski
    Pharmacology, Global Preclinical Development, R & D, Bausch & Lomb, Rochester, New York
  • A. Shafiee
    Pharmacology, Global Preclinical Development, R & D, Bausch & Lomb, Rochester, New York
  • F. J. López
    Pharmacology, Global Preclinical Development, R & D, Bausch & Lomb, Rochester, New York
  • K. W. Ward
    Pharmacology, Global Preclinical Development, R & D, Bausch & Lomb, Rochester, New York
  • Footnotes
    Commercial Relationships  E. Budzynski, Bausch&Lomb, E; A. Shafiee, Bausch&Lomb, E; F.J. López, Bausch&Lomb, E; K.W. Ward, Bausch&Lomb, E.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 1468. doi:
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      E. Budzynski, A. Shafiee, F. J. López, K. W. Ward; BOL-303242-X, a Selective Glucocorticoid Receptor Agonist (SEGRA), Offers a Better in vivo Side Effect Profile Than Dexamethasone on Intraocular Pressure Elevation in Normotensive Rabbits. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1468.

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

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Abstract

Purpose: : 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 steroids. In this study we evaluated the effect of BOL-303242-X on intraocular pressure (IOP) in normotensive rabbits compared to dexamethasone (DEX).

Methods: : Rabbits were conditioned to morning IOP measurements with a pneumotonometer for two weeks (baseline IOP = 24.3 ± 1.8 mmHg) prior to dosing. After the conditioning period, animals were divided into five groups and the right eyes were treated topically four times per day with one of the following: PBS, DEX (0.5 mg), BOL-303242-X (0.05, 0.25, or 0.5 mg) for 30 days. IOP was measured three times per week between 7-10 am. Data were analyzed by a two-way ANOVA with repeated measures followed by the contrast procedure in JMP (SAS Institute; Cary, NC). In order to obtain an integrated response over time, the area under the curve (AUC) was calculated for each IOP time-profile using the trapezoidal rule. These data were then analyzed using one-way ANOVA followed by Dunnett’s test to compare differences between treatment groups versus the PBS-treated group.

Results: : DEX-treated animals showed significantly greater IOP on days 12-26 compared to PBS-treated animals. Rabbits treated with 0.05 mg BOL-303242-X showed no significant effect on IOP, whereas the rabbits treated with 0.25 mg BOL-303242-X showed significantly greater IOP than PBS on days 16, 18, 24, and 26, and at the highest dose tested IOP was greater than that of PBS-treated animals only on day 26. Evaluation of the integrated responses over time (AUC) revealed that no dose of BOL-303242-X changed IOP AUC (mm Hg•day) when compared to PBS treated animals. However, IOP AUC for DEX-treated animals was significantly greater than that of the PBS-treated group.

Conclusions: : These data indicate that overall BOL-303242-X, a SEGRA, has a better safety profile than DEX and may therefore offer a better therapeutic index for conditions that may require chronic ocular treatment with GR agonists.

Keywords: outflow: trabecular meshwork • inflammation 
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