Beauregard Clay, Stephens Donna, Roberts Leighann, Gamache Daniel, Yanni John
External Disease Research, Ophthalmology Discovery, Alcon Research, Ltd., Fort Worth, TX, USA.
J Ocul Pharmacol Ther. 2007 Aug;23(4):315-20. doi: 10.1089/jop.2006.0138.
The topical application of 0.1% olopatadine has been shown to provide significant attenuation of histamine-induced conjunctival vascular permeability (CVP) within 5 min and for as long as 24 h following a topical administration. The duration of the action of olopatadine was compared to that of epinastine, azelastine, and ketotifen. Male Hartley outbred guinea pigs (weighing 250-300 g) were administered a drug or vehicle as single O.D. topical drops, at times ranging from 4 to 24 h prior to histamine challenge. One (1) h prior to histamine challenge, the animals were administered 1 mL of Evans blue dye (1 mg/mL) through the marginal ear vein. Histamine (300 ng) was administered by a subconjunctival injection, and the guinea pigs were sacrificed 30 min later. CVP was assessed as the area and color intensity stained with Evans blue dye. The potencies of each drug were determined by calculating a 50% effective dose (ED(50)) for the inhibition of vascular leakage, compared to vehicle treatment, at each time point. Olopatadine was the only compound tested that was significantly effective 16 h following a single topical application. The ED(50) for olopatadine at 16 h was 0.031%. Epinastine, azelastine, and ketotifen were only significantly effective for up to 4 h. Olopatadine exhibited the longest duration of action for inhibition of histamine-induced vascular permeability in guinea pigs of any topical antiallergic drug tested. Concentrations of olopatadine, which provided a greater than 50% inhibition of the histamine-induced vascular response, were consistently less than 0.1% over a 16-h pretreatment interval.
0.1%奥洛他定局部应用已显示，在局部给药后5分钟内及长达24小时内，能显著减轻组胺诱导的结膜血管通透性（CVP）。将奥洛他定的作用持续时间与依匹斯汀、氮卓斯汀和酮替芬的作用持续时间进行了比较。雄性Hartley远交豚鼠（体重250 - 300克）在组胺激发前4至24小时的不同时间，通过单眼局部滴注给予药物或赋形剂。在组胺激发前1小时，通过耳缘静脉给予动物1毫升伊文思蓝染料（1毫克/毫升）。通过结膜下注射给予组胺（300纳克），30分钟后处死豚鼠。CVP通过伊文思蓝染料染色的面积和颜色强度进行评估。与赋形剂处理相比，通过计算每个时间点抑制血管渗漏的50%有效剂量（ED50）来确定每种药物的效力。奥洛他定是唯一一种单次局部应用后16小时仍显著有效的受试化合物。奥洛他定在16小时时的ED50为0.031%。依匹斯汀、氮卓斯汀和酮替芬仅在长达4小时内显著有效。在受试的任何局部抗过敏药物中，奥洛他定对组胺诱导的豚鼠血管通透性抑制作用的持续时间最长。在16小时的预处理间隔内，能提供大于50%组胺诱导血管反应抑制作用的奥洛他定浓度始终低于0.1%。
