Pharmacologic characteristics and adrenal suppression with newer inhaled corticosteroids: A comparison of ciclesonide and fluticasone propionate

• Published in: Clinical therapeutics Vol. 28; no. 3; pp. 319 - 331
• Main Author: Kaliner, Michael A.
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01.03.2006; Excerpta Medica; Elsevier Limited
• Subjects: Adrenal Cortex Hormones - pharmacology; Adrenal Cortex Hormones - therapeutic use; adrenal suppression; Androstadienes - pharmacology; Androstadienes - therapeutic use; Asthma; Asthma - drug therapy; Asthma - physiopathology; Biological and medical sciences; Bone density; Cataracts; Childrens health; Chronic obstructive pulmonary disease, asthma; ciclesonide; Fluticasone; fluticasone propionate; Fractures; Glaucoma; Half-Life; Humans; Hypothalamo-Hypophyseal System - drug effects; Hypothalamo-Hypophyseal System - physiopathology; inhaled corticosteroids; Medical sciences; Metabolism; Metered Dose Inhalers; Ophthalmology; Pharmacodynamics; Pharmacokinetics; Pharmacology. Drug treatments; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - physiopathology; Pneumology; Pregnenediones - pharmacology; Pregnenediones - therapeutic use; Steroids; Thorax; adrenal suppression; asthma; ciclesonide; fluticasone propionate; inhaled corticosteroids; Lung disease; Corticosteroid; Adrenal glands; Respiratory disease; Antiinflammatory agent; Fluticasone; Antiasthma agent; Asthma; Inhalation; Bronchus disease; Obstructive pulmonary disease; Ciclesonide; Comparative study
• DOI: 10.1016/j.clinthera.2006.03.003
• ISSN: 0149-2918

Inhaled corticosteroids (ICSs) are the most potent anti-inflammatory choice for patients with asthma. Selecting the most appropriate ICS for a patient requires a thorough understanding of the pharmacologic properties of each drug. This review details the pharmacologic properties of ciclesonide (CIC) and fluticasone propionate (FP) and reviews the available data on suppression of the hypothalamic-pituitary-adrenal axis as a measure of systemic exposure and safety profile. Clinical studies and case reports wereidentified through a MEDLINE and EMBASE search of English-language articles. The databases were searched for the years 1990 to April 2005 using the terms ciclesonide, fluticasone, ICS, and adrenal suppression. All studies were clinical trials of pharmacologic properties of the ICSs in humans. A total of 1082 articles were identified. CIC and FP are 2 of the most potent ICSs. Both have high receptor-binding affinities (12 times and 18 times that of dexamethasone, respectively), and both may provide enhanced respiratory effects through a prolonged pulmonary residence time. The CIC metered dose inhaler dispenses smaller and more highly respirable particles than FP (1.1–2.1 pm vs 2.8–3.2 μm, respectively). Therefore, a greater percentage of administered CIC is topically deposited in the lungs (52% vs 12% to 13% for FP). CIC is delivered as aninactive parent compound, which is converted to its active metabolite, desisobutyryl-CIC (des-CIC), by esterases in the airways. More than 50% of a dose of CIC is deposited and distributed evenly throughout the lungs of healthy adults; lipid conjugation in the lung also may increase lung residence time. On entering the systemic circulation, both corticosteroids are rapidly cleared by the liver (elimination half-life of 3.5 hours for CIC vs 7.8 hours for FP). However, plasma protein binding is greater with CIC/des-CIC (99%/≈99%) than FP (90%), resulting in reduced amounts of des-CIC (<I%) versus FP (10%) circulating free in the plasma. Although studies of low or medium doses of FP have produced conflicting results, high doses of FP (>660 pg/d) may result in adrenal suppression. CIC has not been reported to produce any significant adrenal suppression throughout its studied dose range (up to 1280 μ/d). A review of the literature suggests that CIC, as compared with FP, achieves greater pulmonary deposition, causes fewer adverse oropharyngeal effects, deposits less biologically active drug in the systemic circulation, and has less potential for adrenal suppression.