Research article

Uptake and metabolism of ciclesonide and retention of desisobutyryl-ciclesonide for up to 24 hours in rabbit nasal mucosa

Hideyuki Sato¹ , Ruediger Nave² , Takashi Nonaka¹ , Nishibe Yoshihisa¹ , Nagano Atsuhiro¹ , Tsutomu Mochizuki¹ , Shigehiro Takahama¹ , Shiro Kondo¹ and Mark Wingertzahn³

¹Teijin Institute for Biomedical Research, TEIJIN Pharma Limited, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512, Japan

²ALTANA Pharma AG, Byk-Gulden-Str. 2, 78467 Konstanz, Germany

³ALTANA Pharma, 220 Park Avenue, Florham Park, NJ 07932, USA

author email corresponding author email

BMC Pharmacology 2007, 7:7doi:10.1186/1471-2210-7-7

Published:	6 June 2007

Abstract

Background

The nasal tissue uptake and metabolism of ciclesonide, a new-generation corticosteroid under investigation for treatment of allergic rhinitis, to its active metabolite, desisobutyryl-ciclesonide (des-CIC), was evaluated when administered to rabbits in a hypotonic versus an isotonic ciclesonide suspension. Nasal mucosa extracts from normal Japanese white rabbits were evaluated by high-performance liquid chromatography with tandem mass spectrometry detection after a single 143-μg dose of ciclesonide. Retention and formation of fatty acid conjugates of des-CIC were also measured in nasal mucosa extracts postadministration of a hypotonic ciclesonide suspension (143-μg single dose).

Results

Versus an isotonic suspension, the hypotonic suspension achieved higher concentrations of des-CIC (5.6-fold, 11.4-fold, and 13.4-fold; p < 0.05 for all) and ciclesonide (25.3-fold, 34.2-fold [p = not significant], and 16-fold [p < 0.05]) at 30, 120, and 240 min postadministration. Additionally, when administered via a hypotonic suspension, des-CIC was retained up to 24 h postadministration (45.46 pmol/g tissue). Highest concentration of major fatty acid ester conjugate, des-CIC-oleate, was detected in nasal mucosa at 8 h postadministration.

Conclusion

These data suggest that a hypotonic ciclesonide suspension provides higher intracellular concentrations of des-CIC up to 24 h, thereby providing a rationale for investigation of ciclesonide as a convenient once-daily nasal spray for treatment of allergic rhinitis.