In vitro activation of the corticosteroid ciclesonide in animal nasal mucosal homogenates
| Autor: | Tsutomu Mochizuki, Ruediger Nave, Shiro Kondo, Hideyuki Sato, Shigehiro Takahama, Takashi Nonaka |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Guinea Pigs Pharmaceutical Science Mucous membrane of nose Ciclesonide In Vitro Techniques Pharmacology Tandem mass spectrometry Mass Spectrometry Rats Sprague-Dawley chemistry.chemical_compound Dogs Adrenal Cortex Hormones Pregnenediones Internal medicine medicine Animals Pharmacology (medical) Animal species Biotransformation Chromatography High Pressure Liquid Active metabolite Rhinitis Allergic Seasonal General Medicine Metabolism In vitro Rats Nasal Mucosa Endocrinology chemistry Corticosteroid Rabbits Half-Life |
| Zdroj: | Biopharmaceutics & Drug Disposition. 28:59-64 |
| ISSN: | 1099-081X 0142-2782 |
| DOI: | 10.1002/bdd.531 |
| Popis: | 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 µmol/l (0.271 µg/ml) or 5 µmol/l (2.71 µg/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 µmol/l and 5 µmol/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 µmol/l and 5 µmol/l, respectively. This study confirms that ciclesonide is converted to des-CIC in nasal mucosal homogenates without any marked differences among animal species. Copyright © 2007 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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