The systemic safety of inhaled corticosteroid therapy: a focus on ciclesonide.
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.
Meltzer
Eli O
EO
Allergy and Asthma Medical Group and Research Center, San Diego, California 92123, USA. eomeltzer@aol.com
Derendorf
Hartmut
H
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
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C120481:ciclesonide