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

BMC Pharmacol. 2007 Jun 6;7:7. doi: 10.1186/1471-2210-7-7.


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-mug 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-mug 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.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Anti-Allergic Agents / administration & dosage
  • Anti-Allergic Agents / metabolism
  • Anti-Allergic Agents / pharmacokinetics*
  • Chromatography, High Pressure Liquid
  • Drug Administration Schedule
  • Esters / metabolism
  • Fatty Acids / metabolism
  • Hypotonic Solutions
  • Isotonic Solutions
  • Male
  • Nasal Mucosa / metabolism*
  • Pregnenediones / administration & dosage
  • Pregnenediones / metabolism*
  • Pregnenediones / pharmacokinetics*
  • Rabbits
  • Suspensions
  • Tandem Mass Spectrometry
  • Time Factors


  • Anti-Allergic Agents
  • Esters
  • Fatty Acids
  • Hypotonic Solutions
  • Isotonic Solutions
  • Pregnenediones
  • Suspensions
  • desisobutyrylciclesonide
  • ciclesonide