Nave Rüdiger
Department of Pharmacometrics/Pharmacokinetics, Nycomed GmbH, Konstanz, Germany.
Clin Pharmacokinet. 2009;48(4):243-52. doi: 10.2165/00003088-200948040-00002.
Asthma is a chronic inflammatory disease of the airways, and inhaled corticosteroids (ICSs) are recommended as first-line therapy for persistent asthma of all severities. Ciclesonide is a novel ICS, which is administered as an aerosol solution in a metered-dose inhaler, using hydrofluoroalkane-134a as a propellant. Because of the high respirable particle fraction, high pulmonary deposition is obtained in patients, which constitutes the basis of effective therapeutic action. The parent compound, ciclesonide, is pharmacologically inactive and is activated in the target organ, the lung, to form its only pharmacologically active metabolite, desisobutyryl-ciclesonide (des-CIC). Low oral deposition combined with minimal formation of des-CIC in the oropharynx may minimize the typical oropharyngeal adverse events associated with ICSs. Low oral bioavailability, rapid clearance and high protein binding reduce pharmacologically relevant systemic exposure. The unique pharmacokinetic and pharmacodynamic profile of ciclesonide offers a rationale that supports the favourable risk-benefit profile observed in clinical trials in patients with persistent asthma.
哮喘是一种气道慢性炎症性疾病，吸入性糖皮质激素（ICSs）被推荐作为所有严重程度持续性哮喘的一线治疗药物。环索奈德是一种新型ICS，它以计量吸入器中的气雾剂溶液形式给药，使用氢氟烷烃-134a作为推进剂。由于可吸入颗粒分数高，患者肺部沉积率高，这构成了有效治疗作用的基础。母体化合物环索奈德无药理活性，在靶器官肺中被激活，形成其唯一具有药理活性的代谢产物去异丁酰基环索奈德（des-CIC）。口服沉积率低，结合口咽部des-CIC生成极少，可将与ICSs相关的典型口咽部不良事件降至最低。口服生物利用度低、清除迅速和高蛋白结合率降低了具有药理相关性的全身暴露。环索奈德独特的药代动力学和药效学特征为其在持续性哮喘患者临床试验中观察到的良好风险效益比提供了理论依据。
