Ciclesonide, a new
corticosteroid for
allergic rhinitis, is administered as an inactive parent compound that is converted by
esterases to the pharmacologically active metabolite,
desisobutyryl-ciclesonide (
des-CIC). This study investigated the in vitro activation of
ciclesonide in nasal mucosa of multiple animal species. Nasal mucosal homogenates from rats, guinea-pigs, rabbits and dogs were incubated with
ciclesonide 0.5 micromol/l (0.271 microg/ml) or 5 micromol/l (2.71 microg/ml) for up to 120 min. Concentrations of
ciclesonide and
des-CIC were measured by high-performance liquid chromatography with tandem mass spectrometry.
Ciclesonide was metabolized to
des-CIC in nasal mucosal homogenates of each species. The initial velocities of
des-CIC formation ranged from 0.0038 to 0.0150 nmol/min/mg
protein and 0.0319 to 0.0983 nmol/min/mg
protein in nasal mucosal homogenates incubated with
ciclesonide 0.5 micromol/l and 5 micromol/l, respectively. Furthermore, the initial velocities of
ciclesonide metabolism ranged from 0.0032 to 0.0142 nmol/min/mg
protein and 0.0445 to 0.1316 nmol/min/mg
protein in nasal mucosal homogenates incubated with
ciclesonide 0.5 micromol/l and 5 micromol/l, respectively. This study confirms that
ciclesonide is converted to
des-CIC in nasal mucosal homogenates without any marked differences among animal species.