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C. Beauregard, D. J. Stephens, S. T. Miller, L. Roberts, D. A. Gamache, J. M. Yanni; Comparative Effects of Olopatadine, Bepotastine, and Bilastine on Conjunctival Mast Cell Stabilization and Histamine-Induced Vascular Permeability. Invest. Ophthalmol. Vis. Sci. 2008;49(13):417.
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Olopatadine is a potent and selective histamine H1 receptor antagonist and mast cell stabilizer which is effective against signs and symptoms of allergic conjunctivitis. In the present study we examine the anti-histaminic effects of bepotastine and bilastine in a guinea pig model of histamine-induced conjunctival vascular permeability. We also examine the mast cell stabilizing effects of bepotastine and bilastine in cultured human conjunctival tissue mast cells.
Mast cells were isolated from human donor conjunctival tissue and were pre-treated with drug and stimulated to degranulate by IgE challenge. Total histamine release was measured by EIA. To measure in vivo anti-histaminic activity, guinea pigs were given a subconjunctival histamine challenge after pre-treatment with topical drug or vehicle and i.v. loading with Evans blue dye. The wheal response of dye leakage was measured 30 min after histamine challenge. To measure in vivo mast cell stabilization activity, guinea pigs were passively sensitized to ovalbumin topically challenged on the eye 24 hrs later. Clinical signs of conjunctivitis (congestion/redness, swelling, and discharge/tearing) were scored 30 min after antigen challenge.
With 30 min pre-treatment, bilastine, bepotastine, and olopatadine each significantly inhibited histamine-induced vascular permeability. Bepotastine and bilastine had similar ED50 values (0.028% and 0.034%, respectively), while the ED50 for olopatadine was 0.002%. When bilastine and bepotastine were administered 2 to 8 hrs before histamine challenge, 50% efficacy was not achieved, whereas olopatadine maintained an ED50 below 0.1%. Bepotastine dose-dependently inhibited human conjunctival mast cell degranulation in vitro with an IC50 of 252 µM, whereas olopatadine inhibited degranulation with an IC50 of 559. However at a concentration of 10 mM, bepotastine significantly potentiated histamine release from mast cells, whereas olopatadine did not.
Bepotastine and bilastine, two H1 antagonists in development for topical treatment of allergic conjunctivitis, are topically active anti-histamines in a guinea pig model of vascular permeability and significantly inhibit human conjunctival mast cell degranulation. However, bilastine and bepotastine do not equal the potency or duration of action of olopatadine in vivo. Bepotastine also potentiates mast cell degranulation at high concentrations, suggesting a potential for ocular side effects with frequent dosing.
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