Document Detail

Pharmacologic characteristics and adrenal suppression with newer inhaled corticosteroids: A comparison of ciclesonide and fluticasone propionate.
MedLine Citation:
PMID:  16750447     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: Clinical studies and case reports were identified 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.
RESULTS: 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 microm, 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 an inactive 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%/ approximately 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 micro/d).
CONCLUSIONS: 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.
Michael A Kaliner
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Clinical therapeutics     Volume:  28     ISSN:  0149-2918     ISO Abbreviation:  Clin Ther     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-06-05     Completed Date:  2006-07-07     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  7706726     Medline TA:  Clin Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  319-31     Citation Subset:  IM    
Institute for Asthma and Allergy, Chevy Chase, Maryland 20815, USA.
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MeSH Terms
Adrenal Cortex Hormones / pharmacology*,  therapeutic use
Androstadienes / pharmacology*,  therapeutic use
Asthma / drug therapy*,  physiopathology
Hypothalamo-Hypophyseal System / drug effects*,  physiopathology
Metered Dose Inhalers
Pituitary-Adrenal System / drug effects*,  physiopathology
Pregnenediones / pharmacology*,  therapeutic use
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Androstadienes; 0/Pregnenediones; CUT2W21N7U/fluticasone; S59502J185/ciclesonide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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