Source: Annual Congress 2002 - Asthma and COPD: pharmacology
Disease area: Airway diseases

Abstract

Objectives: Ciclesonide (CIC) is a novel topical glucocorticosteroid currently developed for treatment of asthma. In the present study we investigated the absorption, bioavailability and the excretion of CIC after single oral and intravenous administration in healthy subjects. Methods: In a randomised crossover study, six healthy male subjects (age range: 19-40y) received a single dose of 6.90mg oral and 0.64mg intravenous of ¹⁴C-CIC, separated by a wash-out period of at least 14 days. Concentrations of total radioactivity were determined in whole blood, plasma, faeces, and urine; the serum concentrations of CIC and its active principle CIC-AP were determined by LC/MS/MS. Results: Based on a dose-normalised ¹⁴C-AUC, 24.5% of orally administered ¹⁴C-CIC was absorbed. Following oral administration, CIC was not detected in any of the serum samples and the concentration of CIC-AP was mostly below or near the LLOQ (25ng/l) indicating an almost complete first-pass metabolism. CIC showed no accumulation in the red blood cells. Drug-related material was predominantly excreted via the faeces (oral 77.9%; intravenous 66.0%) and the recovery of total radioactivity was complete 120h after drug intake. Conclusions: Absorption of orally administered CIC is low. Due to an almost complete first-pass metabolism of CIC the systemic bioavailability of the active principle is <1%. Thus, the portion of CIC, which is swallowed after inhalation, does not lead to any relevant change in systemic concentrations.

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Citations should be made in the following way:
R. Nave, T. D. Bethke, S. P. van Marle, K. Zech (Konstanz, Germany; Zuidlaren, The Netherlands). Pharmacokinetics of ¹⁴C-ciclesonide after oral and intravenous administration in healthy subjects. Eur Respir J 2002; 20: Suppl. 38, 745

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