title: Repeated-dose pharmacokinetics of inhaled ciclesonide (CIC-HFA) in Japanese children with bronchial asthma: a phase I study.
abstract: BACKGROUND
  Ciclesonide (CIC) is a highly safe, inhaled corticosteroid (ICS) that is converted into a pharmacologically active metabolite (des-isobutyryl-ciclesonide); this metabolite, in turn, exerts a local anti-inflammatory effect on lung tissue. The present study was undertaken to analyze the pharmacokinetics of des-isobutyryl-ciclesonide in the serum of Japanese children with bronchial asthma treated by repeated doses of CIC and to compare the data thus obtained with those obtained for Caucasian children with bronchial asthma.
  
  
  METHODS
  Eight Japanese children with bronchial asthma were treated for 7 days with CIC-hydrofluoroalkalane (CIC-HFA) 200 μg/day administered by a metered-dose inhaler. The study was designed to assess the pharmacokinetics after 7-day repeated administration by which the steady state can be achieved, based on the results of an earlier study involving healthy Japanese adult males who received 7-day repeated administration of CIC-HFA. Blood was sampled at multiple time points on Day 7 of treatment for measurement of the serum des-isobutyryl-ciclesonide level.
  
  
  RESULTS
  The pharmacokinetic parameters (AUC from time zero to last observed concentration [AUC(t)], AUC over the dosage interval τ at steady state [AUC(ss)], maximum concentration [C(max)], and terminal elimination half-life [T(1/2)]) and the temporal changes in the serum levels of des-isobutyryl-ciclesonide after repeated administration of CIC-HFA (200 μg/day) in Japanese children with bronchial asthma differed only slightly from those in Caucasian children with bronchial asthma. No serious adverse events were noted during the study period. Additionally, no abnormalities were detected in the serum cortisol level, other laboratory parameters, or vital signs.
  
  
  CONCLUSIONS
  Our results suggest that there is little difference in the pharmacokinetics of des-isobutyryl-ciclesonide up on repeated administration of CIC-HFA between Japanese and Caucasian children with bronchial asthma. And our study suggests that CIC-HFA (200 μg/day, once daily) can be administered safely for 7 days, without raising any safety concerns.
authors.affiliation: Department of Pediatric, Gifu University Graduate School of Medicine, Japan. t−tera@gifu−u.ac.jp
authors.forename: Takahide
authors.initials: T
authors.lastname: Teramoto
authors.forename: Eiko
authors.initials: E
authors.lastname: Matsui
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yonezawa
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Kato
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ohnishi
authors.forename: Hideo
authors.initials: H
authors.lastname: Kaneko
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Sankei
authors.initials: S
authors.lastname: Nishima
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D044466:Asian People; D001249:Asthma / Q000188:drug therapy* / Q000208:ethnology / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D036501:Metered Dose Inhalers; D011282:Pregnenediones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C120481:ciclesonide