ISTA Pharmaceuticals, Inc., Irvine, CA 92618-2600, USA.
Curr Med Res Opin. 2010 Oct;26(10):2329-38. doi: 10.1185/03007995.2010.486753.
The purpose of this review is to examine published non-clinical literature on the antihistamine bepotastine besilate, including pharmacokinetic and pharmacologic properties.
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.
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.
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.
本综述的目的是检查已发表的非临床文献中关于苯海拉明倍他司汀倍他索的内容，包括药代动力学和药理学特性。
使用各种数据库进行标准文献检索，以查找 1997 年至 2009 年期间发表的关于苯海拉明倍他司汀倍他索的文章。这些文章主要描述了用于开发苯海拉明倍他司汀倍他索口服制剂的非临床数据，并且以日文出版。在数据库检索中未发现有关苯海拉明倍他司汀倍他索眼部制剂的非临床数据出版物。
苯海拉明倍他司汀是第二代抗组胺药，具有选择性组胺 H（1）受体拮抗剂活性。苯海拉明对与不良副作用相关的受体（包括组胺 H（3）、α（1）-、α（2）-和β-肾上腺素能、5-羟色胺（5-HT（2））、毒蕈碱和苯二氮䓬受体）的亲和力可忽略不计。苯海拉明具有额外的抗过敏活性，包括稳定肥大细胞功能、抑制嗜酸性粒细胞浸润、抑制白细胞介素-5 产生以及抑制 LTB（4）和 LTD（4）活性。苯海拉明在体内剂量依赖性地抑制组胺诱导的血管通透性加速，并抑制豚鼠研究中的同源性被动皮肤过敏反应。在瘙痒的小鼠模型中，口服苯海拉明抑制搔抓行为的频率和持续时间。多项体内动物毒理学研究表明，苯海拉明安全，对呼吸、循环、中枢神经系统、消化系统或泌尿系统无明显影响。在大鼠中静脉给予苯海拉明倍他司汀（3mg/kg）后，脑中苯海拉明的浓度低于血浆中的浓度，与较老的抗组胺药相比，预测镇静作用降低。
非临床的体外和体内研究表明，苯海拉明是一种组胺 H（1）受体拮抗剂，具有良好的药代动力学、药理学、安全性和抗组胺特性，并且作用于过敏炎症的其他途径，而不仅仅是直接涉及组胺 H（1）受体。
