Kalivas J, Breneman D, Tharp M, Bruce S, Bigby M
Department of Medicine, University of Kansas Medical Center, Kansas City 66103.
J Allergy Clin Immunol. 1990 Dec;86(6 Pt 2):1014-8. doi: 10.1016/s0091-6749(05)80246-5.
Chronic urticaria is a problem for both physician and patient. In an effort to avoid the risks associated with corticosteroid treatment, many first-generation H1-receptor antagonists have been tried and found to induce undesirable levels of sedation when given in amounts sufficient to control urticaria. Cetirizine, a pharmacologically active oxidized metabolite of hydroxyzine, was developed to provide selective H1-receptor inhibition without depression of the central nervous system. In a 4-week, multicenter, double-blind, placebo-controlled safety and efficacy study, cetirizine, in a once-a-day dose (5 to 20 mg), was equivalent in efficacy to hydroxyzine in divided doses (25 to 75 mg/day). The incidence of somnolence in the cetirizine group was not significantly different from that of the placebo group. However, in the hydroxyzine group, the incidence of somnolence was significantly higher than that in the placebo group (p = 0.001). The results of this study demonstrate that cetirizine has a greater safety margin over the older parent drug hydroxyzine.
慢性荨麻疹对医生和患者来说都是个问题。为了避免与皮质类固醇治疗相关的风险,人们尝试了许多第一代H1受体拮抗剂,结果发现,当给予足以控制荨麻疹的剂量时,这些药物会引起不良程度的镇静作用。西替利嗪是羟嗪的一种具有药理活性的氧化代谢产物,其研发目的是在不抑制中枢神经系统的情况下提供选择性H1受体抑制作用。在一项为期4周的多中心、双盲、安慰剂对照的安全性和疗效研究中,西替利嗪每日一次给药(5至20毫克),其疗效与分剂量给药(25至75毫克/天)的羟嗪相当。西替利嗪组嗜睡的发生率与安慰剂组无显著差异。然而,在羟嗪组中,嗜睡的发生率显著高于安慰剂组(p = 0.001)。这项研究的结果表明,与旧的母体药物羟嗪相比,西替利嗪具有更大的安全边际。