Pharmacokinetic disposition of inhaled ciclesonide and its metabolite desisobutyryl-ciclesonide in healthy subjects and patients with asthma are similar.
OBJECTIVE
To evaluate whether the inflammatory process and bronchial constriction associated with asthma influence the pulmonary distribution and airway penetration of inhaled ciclesonide by investigating the pharmacokinetics of ciclesonide and its active metabolite, desisobutyryl-ciclesonide (des-CIC) in patients with asthma and matched healthy subjects.


METHODS
12 patients with asthma (8 males, 4 females) and 12 healthy subjects matched for age, sex, height, and weight received a single inhaled dose of 1,280 microg (ex-actuator, equivalent to 1,600 microg ex-valve) ciclesonide by metered-dose inhaler in a parallel-group study. Timed blood samples were collected for measurement of serum concentrations of des-CIC and ciclesonide by liquid chromatography with tandem mass spectrometry.


RESULTS
There were no differences in the pharmacokinetics of des-CIC between healthy subjects and patients with asthma. Ratio analysis of the primary variable, the area under the concentration-time curve from time 0 to infinity (AUC(0 - inf)) showed equivalence for des-CIC in healthy subjects and patients with asthma, with a ratio of 1.003 (90% confidence interval between 0.815 and 1.234). The mean terminal half-life (t1/2) for des-CIC was also similar in patients with asthma (3.15 hours) and healthy subjects (3.33 hours). Furthermore, the pharmacokinetic parameter estimates for ciclesonide were comparable between the study groups.


CONCLUSIONS
After administration of a single dose of ciclesonide, the pharmacokinetic parameter estimates for des-CIC were equivalent between patients with mild-to-moderate asthma and healthy subjects, suggesting that there is comparable lung deposition and activation of ciclesonide in the 2 populations.
Nave
R
R
Drug Metabolism and Pharmacokinetics, ALTANA Pharma AG, Byk-Gulden-Strasse 2, 78467 Konstanz, Germany. ruediger.nave@altanapharma.com
Gunawardena
K A
KA
Zech
K
K
Bethke
T D
TD
D000280:Administration, Inhalation; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011282:Pregnenediones / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D018927:Anti-Asthmatic Agents; D000893:Anti-Inflammatory Agents; D011282:Pregnenediones; C494355:desisobutyrylciclesonide; C120481:ciclesonide