Derendorf Hartmut
Department of Pharmaceutics, University of Florida, Gainesville, FL 32610, USA.
J Clin Pharmacol. 2007 Jun;47(6):782-9. doi: 10.1177/0091270007299763. Epub 2007 Apr 5.
Inhaled corticosteroids are recommended first-line therapy for persistent asthma of all severities; however, oropharyngeal and systemic adverse events can be a concern. Inhaled corticosteroids exert their therapeutic and adverse effects by interacting with glucocorticoid receptors within and outside the lungs, respectively. Ciclesonide is a novel inhaled corticosteroid that possesses a unique pharmacokinetic and pharmacodynamic profile. Ciclesonide is inactive itself and converted to its pharmacologically active metabolite, desisobutyryl-ciclesonide, in the target organ, the lungs. Pulmonary activation combined with low oral deposition may minimize oropharyngeal adverse events, and low oral bioavailability, rapid clearance, and high protein binding may reduce systemic exposure. In addition, high pulmonary deposition due to the highly respirable particles, combined with the potential for prolonged lung retention via lipid conjugation, provides for effective therapeutic action.
吸入性糖皮质激素被推荐作为所有严重程度持续性哮喘的一线治疗药物；然而，口咽和全身不良事件可能令人担忧。吸入性糖皮质激素分别通过与肺内外的糖皮质激素受体相互作用发挥其治疗作用和不良反应。环索奈德是一种新型吸入性糖皮质激素，具有独特的药代动力学和药效学特征。环索奈德本身无活性，在靶器官肺中转化为其药理活性代谢产物去异丁酰基环索奈德。肺部激活与低口服沉积相结合可使口咽不良事件降至最低，而低口服生物利用度、快速清除和高蛋白结合可能会减少全身暴露。此外，由于颗粒具有高可吸入性导致的高肺部沉积，以及通过脂质结合实现的肺部长期滞留可能性，提供了有效的治疗作用。
