David Geffen School of Medicine at UCLA , 10833 Le Conte Ave, Los Angeles, CA 90095 , USA +1 310 825 3163 ; +1 310 206 5088 ;
Expert Opin Pharmacother. 2014 Jan;15(1):85-96. doi: 10.1517/14656566.2013.837159. Epub 2013 Sep 14.
Chronic obstructive pulmonary disease (COPD) is a progressive disease, the clinical course of which is punctuated by acute exacerbations. While long-acting bronchodilators and inhaled corticosteroids can reduce exacerbations, some patients do not respond adequately to these agents. Roflumilast , a novel orally active, once-daily phophodiesterase-4-selective inhibitor with anti-inflammatory properties, has been shown to reduce exacerbations and has been approved for the treatment of the subset of COPD patients with symptoms of chronic cough and sputum who have a history of exacerbations.
This article describes the pre-clinical and clinical pharmacology of roflumilast and analytically reviews the published data from the most relevant Phase-II and -III clinical trials evaluating its efficacy and safety.
Roflumilast is the first drug specifically targeted to a particular subset of the heterogeneous population of COPD patients, namely those with chronic bronchitis in addition to severe airflow obstruction and an exacerbation history. Its efficacy in reducing exacerbations in patients already receiving a LABA or anticholinergic bronchodilator underscores its potential utility as an add-on agent in patients who continue to experience exacerbations despite treatment with other agents. Adverse events include gastrointestinal side effects, most commonly, as well as unexplained weight loss.
慢性阻塞性肺疾病（COPD）是一种进行性疾病，其临床过程中伴有急性加重。虽然长效支气管扩张剂和吸入性皮质类固醇可以减少加重，但有些患者对这些药物反应不足。罗氟司特是一种新型的、每日一次的、具有抗炎作用的、口服活性的磷酸二酯酶-4 选择性抑制剂，已被证明可以减少加重，并已被批准用于治疗有慢性咳嗽和咳痰症状且有加重史的 COPD 患者亚群。
本文描述了罗氟司特的临床前和临床药理学，并对评估其疗效和安全性的最相关的 II 期和 III 期临床试验的已发表数据进行了分析性回顾。
罗氟司特是专门针对 COPD 患者异质人群中特定亚群的第一种药物，即除严重气流阻塞和加重病史外，还有慢性支气管炎的患者。它在减少已接受长效β激动剂或抗胆碱能支气管扩张剂治疗的患者的加重方面的疗效，突出了它作为其他药物治疗后仍有加重的患者的附加治疗药物的潜在用途。不良反应包括胃肠道副作用，最常见的是不明原因的体重减轻。
