Bepotastine besilate, a highly selective histamine H1 receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models

Kida, Tetsuo; Fujii, Atsuko; Sakai, Osamu; Iemura, Masahito; Atsumi, Ikuyo; Wada, Tomoyuki; Sakaki, Hideyuki

doi:10.1016/j.exer.2010.04.006

Cited by 34 publications

(17 citation statements)

References 23 publications

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“…The anti-inflammatory actions of bepotastine besilate include inhibition of leukotriene B418 and attenuating eosinophil chemotaxis and activation 13–17. Bepotastine has also been shown to inhibit the biosynthesis of proinflammatory IL-5 in vitro 19. Oral formulations of bepotastine besilate have been well-characterized in Japan in both preclinical13,15–17 and clinical reports,20–23 as well as in several clinical safety studies 24–26.…”

Section: Introductionmentioning

confidence: 99%

Treatment of allergic conjunctivitis with bepotastine besilate ophthalmic solution 1.5%

Bergmann

Williams²,

Gomes

2014

OPTH

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PurposeTo examine the pooled per-protocol ocular end points from two conjunctival allergen challenge (CAC) clinical trials of the dual-action antihistamine bepotastine besilate ophthalmic solution (BBOS) 1.5%.MethodsTwo Phase III, placebo-controlled, double-masked, randomized clinical trials were conducted at a total of six separate centers using the CAC model of allergic conjunctivitis. The same study design was employed for both clinical trials, with subjects randomly assigned to either BBOS 1.5% (n=78) or placebo (n=79) treatment. Each subject received one eye drop of the test agent bilaterally at different study visits 15 minutes, 8 hours, or 16 hours prior to a CAC. Primary ocular end points included changes in ocular itching reported at 3, 5, and 7 minutes and conjunctival hyperemia assessed at 7, 15, and 20 minutes following each CAC. Secondary ocular end points included chemosis as well as episcleral and ciliary hyperemia judged by investigators, and tearing (scored as either absent or present) and eyelid swelling judged by subjects.ResultsA statistically significant reduction in ocular itching was observed for BBOS 1.5% treatment compared to placebo at all time points (P<0.0001), while measures for onset and 8-hour persistence of action also reached clinical significance (ie, ≥1.0 unit difference) at a majority of time points. In addition, a significant reduction in conjunctival hyperemia was achieved at a majority of time points during the onset of action CAC test. Secondary end points were also significantly improved compared to placebo, most prominently for reduced tearing at all study visits and reduced eyelid swelling at the onset of action and 8-hour study visits. Adverse events were generally mild and transient.ConclusionBBOS 1.5% rapidly reduced CAC-induced ocular itching with duration of effectiveness of at least 8 hours after dosing. Certain secondary signs of inflammation were also significantly reduced.

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Section: Introductionmentioning

confidence: 99%

Treatment of allergic conjunctivitis with bepotastine besilate ophthalmic solution 1.5%

Bergmann

Williams²,

Gomes

2014

OPTH

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“…Some of the third generation antihistamines inhibit the vacuolization and accumulation of eosinophils after allergen challenge and directly inhibit eosinophils in vitro (Rothenberg and Hogan, 2006). Bepotastine, an antihistamine with mast cell-stabilizing activity, also has been shown to inhibit the late phase reaction through multiple mechanisms including histamine H 1 receptor antagonism, mast cell stabilization, and inhibition of eosinophil migration to ocular inflammatory sites (Kida et al, 2010). Rupatadine is a selective and long-acting new drug with a strong antagonistic activity toward both histamine H1 receptors and platelet-activating factor receptors.…”

Section: Cell Adhesion-based Therapeutic Strategiesmentioning

confidence: 99%

Therapeutic Targeting of Eosinophil Adhesion and Accumulation in Allergic Conjunctivitis

Baiula¹,

Bedini²,

Carbonari³

et al. 2012

Front. Pharmacol.

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Considerable evidence indicates that eosinophils are important effectors of ocular allergy. Increased worldwide prevalence of allergic eye pathologies has stimulated the identification of novel drug targets, including eosinophils and adhesion molecules. Accumulation of eosinophils in the eye is a key event in the onset and maintenance of allergic inflammation and is mediated by different adhesion molecules. Antihistamines with multiple mechanisms of action can be effective during the early and late phases of allergic conjunctivitis by blocking the interaction between β1 integrins and vascular cell adhesion molecule (VCAM)-1. Small molecule antagonists that target key elements in the process of eosinophil recruitment have been identified and reinforce the validity of α4β1 integrin as a therapeutic target. Glucocorticoids are among the most effective drugs for ocular allergy, but their use is limited by adverse effects. Novel dissociated glucocorticoids can prevent eosinophil accumulation and induce apoptosis of eosinophils, making them promising candidates for ophthalmic drugs. This article reviews recent understanding of the role of adhesion molecules in eosinophil recruitment in the inflamed conjunctiva along with effective treatments for allergic conjunctivitis.

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“…For example, in vitro studies suggest that bepotastine specifically suppresses proinflammatory cytokine production by keratinocytes, including inhibition of CD54 expression 12. Recent work on guinea pigs showed that bepotastine, along with several other H 1 -antihistamines, reduces vascular hyper-permeability in both antigen-induced and histamine-induced hyperpermeability models 13. This work also showed that bepotastine inhibits in vitro eosinophil chemotaxis induced by leukotriene B 4 , and pretreatment with bepotastine limits conjunctival eosinophil infiltration after topical platelet-activating factor instillation 13…”

Section: Review Of Pharmacology Mode Of Action and Pharmacokineticsmentioning

confidence: 99%

Critical appraisal of bepotastine in the treatment of ocular itching associated with allergic conjunctivitis

Wingard

Mah

2011

OPTH

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Bepotastine besilate 1.5% solution is an H1-antihistamine recently approved by the Food and Drug Administration for the topical treatment of ocular itching associated with allergic conjunctivitis. Several clinical studies have demonstrated its safety as well as its efficacy versus placebo. This review finds that bepotastine besilate 1.5% solution is a suitable alternative to other agents within the class of H1-antihistamines, but there are no clinical trial data to suggest that it holds any specific advantages over other agents.

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Bepotastine besilate, a highly selective histamine H1 receptor antagonist, suppresses vascular hyperpermeability and eosinophil recruitment in in vitro and in vivo experimental allergic conjunctivitis models

Cited by 34 publications

References 23 publications

Treatment of allergic conjunctivitis with bepotastine besilate ophthalmic solution 1.5%

Treatment of allergic conjunctivitis with bepotastine besilate ophthalmic solution 1.5%

Therapeutic Targeting of Eosinophil Adhesion and Accumulation in Allergic Conjunctivitis

Critical appraisal of bepotastine in the treatment of ocular itching associated with allergic conjunctivitis

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