Mullol J, Bousquet J, Bachert C, Canonica W G, Gimenez-Arnau A, Kowalski M L, Martí-Guadaño E, Maurer M, Picado C, Scadding G, Van Cauwenberge P
Unitat de Rinologia, Servei d'ORL, Hospital Clinic, IDIBAPS, Barcelona, Spain.
Allergy. 2008 Apr;63 Suppl 87:5-28. doi: 10.1111/j.1398-9995.2008.01640.x.
Histamine is the primary mediator involved the pathophysiology of allergic rhinitis and chronic urticaria, and this explains the prominent role that histamine H(1)-receptor antagonists have in the treatment of these disorders. However, histamine is clearly not the only mediator involved in the inflammatory cascade. There is an emerging view that drugs which can inhibit a broader range of inflammatory processes may prove to be more effective in providing symptomatic relief in both allergic rhinitis and chronic urticaria. This is an important consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative which provides a scientific basis for defining what are the desirable properties of an 'ideal' antihistamine. In this review of rupatadine, a newer dual inhibitor of histamine H(1)- and PAF-receptors, we evaluate the evidence for a mechanism of action which includes anti-inflammatory effects in addition to a powerful inhibition of H(1)- and PAF-receptors. We assess this in relation to the clinical efficacy (particularly the speed of onset of action) and safety of rupatadine, and importantly its longer term utility in everyday life. In clinical trials, rupatadine has been shown to be an effective and well-tolerated treatment for allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of action, producing rapid symptomatic relief, and it also has an extended duration of clinical activity which allows once-daily administration. In comparative clinical trials rupatadine was shown to be at least as effective as drugs such as loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms in adult/adolescent patients with seasonal, perennial or persistent allergic rhinitis. Importantly, rupatadine demonstrated no adverse cardiovascular effects in preclinical or extensive clinical testing, nor negative significant effects on cognition or psychomotor performance (including a practical driving study). It improved the overall well-being of patients with allergic rhinitis or CIU based on findings from quality of life questionnaires and patient global rating scores in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of histamine H(1)- and PAF-receptors, which has been shown to be an effective and generally well-tolerated treatment for allergic rhinitis and chronic urticaria. It possesses a broader profile of anti-inflammatory properties inhibiting both inflammatory cells and a range of mediators involved in the early- and late-phase inflammatory response, but the clinical relevance of these effects remain to be clarified.
组胺是参与变应性鼻炎和慢性荨麻疹病理生理学的主要介质，这就解释了组胺H(1)受体拮抗剂在治疗这些疾病中所起的重要作用。然而，组胺显然不是参与炎症级联反应的唯一介质。一种新出现的观点认为，能够抑制更广泛炎症过程的药物可能在缓解变应性鼻炎和慢性荨麻疹的症状方面更有效。这是变应性鼻炎及其对哮喘的影响（ARIA）倡议的一个重要考虑因素，该倡议为确定“理想”抗组胺药的理想特性提供了科学依据。在这篇关于新型组胺H(1)和PAF受体双重抑制剂卢帕他定的综述中，我们评估了其作用机制的证据，该机制除了对H(1)和PAF受体有强大的抑制作用外，还包括抗炎作用。我们根据卢帕他定的临床疗效（特别是起效速度）和安全性，以及重要的是其在日常生活中的长期效用进行评估。在临床试验中，卢帕他定已被证明是治疗变应性鼻炎和慢性特发性荨麻疹（CIU）的一种有效且耐受性良好的药物。它起效迅速，能迅速缓解症状，并且临床活性持续时间延长，允许每日一次给药。在比较临床试验中，卢帕他定在减轻季节性、常年性或持续性变应性鼻炎的成年/青少年患者的过敏症状方面，被证明至少与氯雷他定、西替利嗪、地氯雷他定和依巴斯汀等药物一样有效。重要的是，卢帕他定在临床前或广泛的临床试验中均未显示出不良心血管影响，对认知或精神运动表现也无显著负面影响（包括一项实际驾驶研究）。根据生活质量问卷和临床试验中患者总体评分的结果，它改善了变应性鼻炎或CIU患者的整体健康状况。因此，卢帕他定是一种最近引入的组胺H(1)和PAF受体双重抑制剂，已被证明是治疗变应性鼻炎和慢性荨麻疹的一种有效且通常耐受性良好的药物。它具有更广泛的抗炎特性，可以抑制炎症细胞以及一系列参与早期和晚期炎症反应的介质，但这些作用的临床相关性仍有待阐明。
