Berger William E
Allergy and Asthma Associates, 27800 Medical Center Road, Mission Viejo, CA 92691, USA.
Curr Drug Saf. 2006 Aug;1(3):265-70. doi: 10.2174/157488606777934422.
Inhaled corticosteroids (ICS) are recommended first-line therapy for patients with asthma of all severities. Prolonged exposure to high-dose ICS can cause systemic and oropharyngeal adverse events. Minimizing ICS-related adverse events by selecting an ICS with an improved safety profile may increase patients' adherence to their asthma treatment. Ciclesonide, a novel ICS currently under development, is a parent compound that is converted in the lungs by endogenous esterases to its active metabolite, desisobutyryl-ciclesonide. Reported data suggest that ciclesonide is well tolerated, with no observed effect on hypothalamic-pituitary-adrenal (HPA)-axis function and a low incidence of oropharyngeal adverse events (comparable with placebo). These safety benefits, observed in children and adults with asthma, may be due to ciclesonide's favorable pharmacokinetic/pharmacodynamic properties. The lack of HPA-axis function suppression may be due to the low oral bioavailability, high serum protein binding and rapid apparent systemic clearance reported with desisobutyryl-ciclesonide. The low incidence of oropharyngeal adverse events may be attributed to the low oral deposition of ciclesonide in the oropharynx and its limited conversion to desisobutyryl-ciclesonide. The favorable safety profile of ciclesonide suggests a conferred benefit to asthma patients treated with this novel ICS.
吸入性糖皮质激素（ICS）被推荐为所有严重程度哮喘患者的一线治疗药物。长期暴露于高剂量ICS可导致全身和口咽不良事件。通过选择具有改善安全性的ICS来尽量减少与ICS相关的不良事件，可能会提高患者对哮喘治疗的依从性。环索奈德是一种目前正在研发的新型ICS，它是一种母体化合物，在肺中被内源性酯酶转化为其活性代谢产物去异丁酰基环索奈德。报告的数据表明，环索奈德耐受性良好，对下丘脑-垂体-肾上腺（HPA）轴功能无观察到的影响，且口咽不良事件发生率低（与安慰剂相当）。在哮喘儿童和成人中观察到的这些安全性益处，可能归因于环索奈德良好的药代动力学/药效学特性。缺乏对HPA轴功能的抑制作用可能是由于去异丁酰基环索奈德报告的口服生物利用度低、血清蛋白结合率高和明显的全身清除率快。口咽不良事件发生率低可能归因于环索奈德在口咽中的口服沉积低及其向去异丁酰基环索奈德的有限转化。环索奈德良好的安全性表明，使用这种新型ICS治疗的哮喘患者可从中获益。
