title: The systemic safety of inhaled corticosteroid therapy: a focus on ciclesonide.
abstract: OBJECTIVE
  To review the potential systemic activity of ciclesonide and its active metabolite, desisobutyryl-ciclesonide, by evaluation of the effects on hypothalamic-pituitary-adrenal (HPA) axis function.
  
  
  METHODS
  EMBASE and MEDLINE searches using the keyword ciclesonide, without date restrictions, were conducted to identify published articles that related to clinical trials that included ciclesonide.
  
  
  METHODS
  The primary articles that reported systemic safety data for ciclesonide were reviewed.
  
  
  RESULTS
  Ciclesonide (320-1,280 microg/d) demonstrated no detectable, clinically relevant effect on HPA axis function as evaluated by basal cortisol excretion measurements and dynamic stimulation tests. Furthermore, ciclesonide had no effect on the normal diurnal rhythm of endogenous cortisol secretion while simultaneously improving pulmonary function and reducing bronchial hyperresponsiveness. These results suggest that ciclesonide has a low systemic activity that may be attributable to unique pharmacologic properties, including a high degree of serum protein binding, a low oral bioavailability, and rapid systemic elimination, that reduce the level of systemically available pharmacologically active drug.
  
  
  CONCLUSIONS
  Even at the higher doses used to treat more severe cases of asthma, ciclesonide was observed to have no effect on HPA axis function. These data, in conjunction with the observed clinical efficacy, suggest that ciclesonide may have an improved therapeutic margin compared with some other currently available inhaled corticosteroid treatments and, therefore, the potential to improve therapeutic outcomes.
authors.affiliation: Allergy and Asthma Medical Group and Research Center, San Diego, California 92123, USA. eomeltzer@aol.com
authors.forename: Eli O
authors.initials: EO
authors.lastname: Meltzer
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001249:Asthma / Q000188:drug therapy; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011282:Pregnenediones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C120481:ciclesonide