Comparison of inhaled corticosteroids: an update.
OBJECTIVE
To review the basis for the estimated comparative daily dosages of inhaled corticosteroids for children and adults that are presented in the National Heart, Lung, and Blood Institute's Expert Panel Report 3; in addition, the pharmacodynamic and pharmacokinetic basis for potential clinical differences among inhaled corticosteroids is discussed.


METHODS
A complete MEDLINE search was conducted of human studies of asthma pharmacotherapy published between January 1, 2001, and March 15, 2006, followed by a PubMed search up until August 2008, using ciclesonide, inhaled corticosteroids, and pharmacokinetics as key words. Product information on each inhaled corticosteroid was also included.


METHODS
Comparative clinical trials of inhaled corticosteroids and systematic reviews for efficacy comparisons were evaluated. Extensive literature reviews, meta-analyses, and selected clinical studies that illustrate or represent specific points of view were selected. Pharmacodynamic and pharmacokinetic data extracted from previously published reviews and specific studies were included.


RESULTS
Pharmacodynamic characteristics (glucocorticoid receptor binding) and lung delivery determine the relative clinical efficacy and pharmacokinetic properties (oral bioavailability, lung retention, systemic clearance) and determine comparative therapeutic index of the inhaled corticosteroids. Secondary pharmacokinetic differences (intracellular fatty acid esterification, high serum protein binding) that have been posited to improve duration of action and/or therapeutic index are unproven, and current comparative clinical trials do not support the hypotheses that they provide an advantage. Ultrafine particle meter-dose inhalers (MDIs) have not demonstrated superior asthma control or improved safety over older MDIs. All of the inhaled corticosteroids demonstrate efficacy with once-daily dosing, and all are more effective when dosed twice daily.


CONCLUSIONS
Current evidence suggests that all of the inhaled corticosteroids have sufficient therapeutic indexes to provide similar efficacy and safety in low to medium doses. Whether or not some of the newer inhaled corticosteroids offer any advantages at higher doses has yet to be determined.
Kelly
H William
HW
University of New Mexico Health Sciences Center, Children's Hospital of New Mexico, 2211 Lomas Blvd. NE, Albuquerque, NM 87131, USA. hwkelly@unm.edu
D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000328:Adult; D018926:Anti-Allergic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004347:Drug Interactions; D006801:Humans; D009330:Nebulizers and Vaporizers; D011282:Pregnenediones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D018926:Anti-Allergic Agents; D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C120481:ciclesonide