Korsgren Magnus, Andersson Morgan, Borgå Olof, Larsson Lars, Aldén-Raboisson Marie, Malmqvist Ulf, Greiff Lennart
Department of Clinical Pharmacology, Lund University Hospital, Lund, Sweden.
Ann Allergy Asthma Immunol. 2007 Apr;98(4):316-21. doi: 10.1016/S1081-1206(10)60876-9.
Intranasal and oral antihistamines are effective in treating allergic rhinitis. Studies comparing these routes of administration of an antihistamine regarding efficacy and pharmacokinetic profile are lacking.
To compare topical and oral routes of administration of cetirizine regarding efficacy, plasma exudation, and systemic drug levels in a repeated allergen challenge model of allergic rhinitis.
Oral cetirizine dihydrochloride, 10 mg once daily, and topical cetirizine dinitrate in a dose corresponding to 4.4 mg of the dihydrochloride salt twice daily were given to grass pollen-sensitive individuals for 12 days in a double-blind, placebo-controlled, crossover design. Timothy grass pollen allergen challenges were given once daily for 7 days using a nasal spray device. Nasal symptoms and peak inspiratory flow were recorded in the morning, 10 minutes after allergen challenge, and in the evening. The pharmacokinetics of the treatments was monitored in 8 patients. The remaining 28 patients were challenged topically with histamine 12 and 24 hours after the final topical and oral cetirizine doses, respectively. Nasal lavage levels of alpha2-macroglobulin were determined to evaluate histamine-induced mucosal plasma exudation.
During the last 3 days of the repeated allergen challenge model, chronic symptoms were established. Both treatments reduced symptoms 10 minutes after allergen challenge (P < .001 vs placebo). Neither treatment reduced morning and evening symptoms or nasal peak inspiratory flow. Topical, but not oral, cetirizine reduced histamine-induced plasma exudation (P < .01 vs placebo) when systemic drug levels were similar in the 2 treatment regimens.
Topical and oral cetirizine reduced acute nasal symptoms produced by allergen challenges in patients with established chronic symptoms. There were also antihistaminic effects of topical cetirizine not related to systemic drug levels.
鼻内和口服抗组胺药对过敏性鼻炎有效。缺乏关于抗组胺药这些给药途径的疗效和药代动力学特征比较的研究。
在过敏性鼻炎的重复变应原激发模型中，比较西替利嗪局部和口服给药途径的疗效、血浆渗出及全身药物水平。
采用双盲、安慰剂对照、交叉设计，给予对草花粉敏感的个体口服10mg盐酸西替利嗪，每日1次，以及局部应用二硝酸西替利嗪，剂量相当于4.4mg盐酸盐，每日2次，共12天。使用鼻喷雾装置每日进行1次梯牧草花粉变应原激发，持续7天。在早晨、变应原激发后10分钟及晚上记录鼻部症状和最大吸气流量。对8例患者监测治疗的药代动力学。其余28例患者在最后一次局部和口服西替利嗪给药后分别于12小时和24小时接受组胺局部激发。测定鼻灌洗中α2-巨球蛋白水平以评估组胺诱导的黏膜血浆渗出。
在重复变应原激发模型的最后3天，出现慢性症状。两种治疗均使变应原激发后10分钟的症状减轻（与安慰剂相比，P <.001）。两种治疗均未减轻早晨和晚上的症状或鼻最大吸气流量。当两种治疗方案的全身药物水平相似时，局部应用而非口服西替利嗪可减轻组胺诱导的血浆渗出（与安慰剂相比，P <.01）。
局部和口服西替利嗪可减轻已出现慢性症状患者变应原激发产生的急性鼻部症状。局部应用西替利嗪还存在与全身药物水平无关的抗组胺作用。
