Giembycz Mark A, Field Stephen K
Department of Physiology and Pharmacology, Faculty of Medicine, University of Calgary, Alberta, Canada.
Drug Des Devel Ther. 2010 Jul 21;4:147-58. doi: 10.2147/dddt.s7667.
In April 2010, the European Medicines Agency Committee for Medicinal Products for Human Use recommended approval of roflumilast, a selective phosphodiesterase 4 inhibitor, for the "maintenance treatment of severe chronic obstructive pulmonary disease (COPD, FEV(1) postbronchodilator less than 50% predicted) associated with chronic bronchitis in adult patients with a history of frequent exacerbations as add-on to bronchodilator treatment". This decision was based, in part, on the results of several large, international, multicenter, randomized, placebo-controlled trials of either six or 12 months' duration that had been undertaken in COPD patients. Roflumilast 500 mug daily improved lung function and reduced exacerbations in patients with more severe COPD, especially those with chronic bronchitis, frequent exacerbations, or who required frequent rescue inhaler therapy in the placebo-controlled trials. It also improved lung function and reduced exacerbations in patients with moderately severe COPD treated with salmeterol or tiotropium. Advantages of roflumilast over inhaler therapy are that it is an oral tablet and only needs to be taken once daily. While taking roflumilast, the most common adverse effects patients experienced were gastrointestinal upset and headache. Weight loss, averaging 2.2 kg, occurred in patients treated with roflumilast. Patients taking roflumilast were more likely to drop out of the trials than patients in the control groups. Patients who discontinued therapy usually did so during the first few weeks and were more likely to have experienced gastrointestinal side effects. Roflumilast is the first selective phosphodiesterase 4 inhibitor and will offer physicians another treatment option for patients with more severe COPD.
2010年4月，欧洲药品管理局人用药品委员会建议批准罗氟司特（一种选择性磷酸二酯酶4抑制剂）用于“作为支气管扩张剂治疗的附加治疗，对有频繁加重病史的成年慢性支气管炎患者的严重慢性阻塞性肺疾病（COPD，支气管扩张剂治疗后FEV(1)低于预测值的50%）进行维持治疗”。这一决定部分基于在COPD患者中进行的几项为期6个月或12个月的大型、国际、多中心、随机、安慰剂对照试验的结果。在安慰剂对照试验中，每日500微克的罗氟司特可改善更严重COPD患者的肺功能并减少病情加重，尤其是那些患有慢性支气管炎、频繁病情加重或需要频繁使用急救吸入器治疗的患者。它还可改善使用沙美特罗或噻托溴铵治疗的中度严重COPD患者的肺功能并减少病情加重。罗氟司特相对于吸入器治疗的优势在于它是口服片剂，且只需每日服用一次。服用罗氟司特时，患者经历的最常见不良反应是胃肠道不适和头痛。接受罗氟司特治疗的患者出现了平均2.2千克的体重减轻。与对照组患者相比，服用罗氟司特的患者更有可能退出试验。停止治疗的患者通常在最初几周内停药，且更有可能经历过胃肠道副作用。罗氟司特是首个选择性磷酸二酯酶4抑制剂，将为医生治疗更严重COPD患者提供另一种治疗选择。
