Pharmacokinetics of [14C]ciclesonide after oral and intravenous administration to healthy subjects

Ciclesonide is a novel inhaled corticosteroid developed for the treatment of asthma. To investigate the extent of oral absorption and bioavailability of ciclesonide referenced to an intravenous infusion. This information provides an estimate for the contribution of the swallowed fraction to systemic...

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Bibliographic Details
Published in:Clinical pharmacokinetics 2004, Vol.43 (7), p.479-486
Main Authors: NAVE, Ruediger, BETHKE, Thomas D, VAN MARLE, Sjoerd P, ZECH, Karl
Format: Article
Language:English
Subjects:
Administration, Oral
Adult
Area Under Curve
Biological and medical sciences
Biological Availability
Bones, joints and connective tissue. Antiinflammatory agents
Cross-Over Studies
Half-Life
Humans
Infusions, Intravenous
Intestinal Absorption
Male
Medical sciences
Pharmacology. Drug treatments
Pregnenediones - administration & dosage
Pregnenediones - blood
Pregnenediones - pharmacokinetics
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Summary:Ciclesonide is a novel inhaled corticosteroid developed for the treatment of asthma. To investigate the extent of oral absorption and bioavailability of ciclesonide referenced to an intravenous infusion. This information provides an estimate for the contribution of the swallowed fraction to systemic exposure to ciclesonide after oral inhalation. In a randomised crossover study, six healthy male subjects (age range 19-40 years) received single doses of 6.9 mg (oral administration) and 0.64 mg (intravenous administration) of [14C]ciclesonide, separated by a washout period of at least 14 days. Total radioactivity was determined in whole blood, plasma, urine and faeces. Serum concentrations of ciclesonide and its major metabolite, the pharmacologically active desisobutyryl-ciclesonide (des-CIC), were determined in serum by high-performance liquid chromatography with tandem mass spectrometry detection. After a 10-minute intravenous infusion, the mean half-life for total radioactivity was 45.2 hours. Elimination of des-CIC was fast with a mean elimination half-life of 3.5 hours. After oral administration, the mean half-life for total radioactivity was 27.5 hours. On the basis of a comparison of dose-normalised areas under the curve of total plasma radioactivity versus time, 24.5% of orally administered [14C]ciclesonide was absorbed. The parent compound ciclesonide was not detected in any of the serum samples after oral administration; serum concentrations of des-CIC were mostly near or below the lower limit of quantification. Thus, systemic bioavailability for des-CIC is
ISSN:0312-5963
1179-1926
DOI:10.2165/00003088-200443070-00004