Non-clinical pharmacology, pharmacokinetics, and safety findings for the antihistamine bepotastine besilate

Scope: The purpose of this review is to examine published non-clinical literature on the antihistamine bepotastine besilate, including pharmacokinetic and pharmacologic properties.

Methods: Standard literature searches using diverse databases were used to find articles on bepotastine besilate published between 1997 and 2009. Articles primarily described non-clinical data utilized for the development of an oral formulation of bepotastine besilate and were published in Japanese. No publications of non-clinical data for an ophthalmic formulation were found in the database searches.

Findings: Bepotastine besilate is a second-generation antihistamine drug possessing selective histamine H(1) receptor antagonist activity. Bepotastine has negligible affinity for receptors associated with undesirable adverse effects, including histamine H(3), α(1)-, α(2)-, and β-adrenergic, serotonin (5-HT(2)), muscarinic, and benzodiazepine receptors. Bepotastine possesses additional anti-allergic activity including stabilization of mast cell function, inhibition of eosinophilic infiltration, inhibition of IL-5 production, and inhibition of LTB(4) and LTD(4) activity. Bepotastine in vivo dose-dependently inhibited the acceleration of histamine-induced vascular permeability and inhibited homologous passive cutaneous anaphylaxis in guinea pig studies. In mouse models of itching, oral bepotastine inhibited the frequency and duration of scratching behavior. Multiple in vivo animal toxicology studies have demonstrated bepotastine to be safe with no significant effects on respiratory, circulatory, central nervous, digestive, or urinary systems. The concentration of bepotastine after intravenous administration of bepotastine besilate (3 mg/kg) in rats was lower in the brain than in plasma, predicting reduced sedation effects compared to older antihistamines.

Conclusion: Non-clinical in vitro and in vivo studies have demonstrated bepotastine is a histamine H(1) receptor antagonist with favorable pharmacokinetic, pharmacologic, safety, and antihistamine properties as well as operating on other pathways leading to allergic inflammation beyond those directly involving the histamine H(1) receptor.