title: In vitro activation of the corticosteroid ciclesonide in animal nasal mucosal homogenates.
abstract: 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.
authors.affiliation: Teijin Institute for Biomedical Research, TEIJIN Pharma Limited, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: R
authors.initials: R
authors.lastname: Nave
authors.forename: T
authors.initials: T
authors.lastname: Nonaka
authors.forename: T
authors.initials: T
authors.lastname: Mochizuki
authors.forename: S
authors.initials: S
authors.lastname: Takahama
authors.forename: S
authors.initials: S
authors.lastname: Kondo
mesh_terms: D000305:Adrenal Cortex Hormones / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006168:Guinea Pigs; D006207:Half-Life; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D011282:Pregnenediones / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D006255:Rhinitis, Allergic, Seasonal / Q000473:pathology
chemical_list: D000305:Adrenal Cortex Hormones; D011282:Pregnenediones; C120481:ciclesonide