title: Ciclesonide: A Pro-Soft Drug Approach for Mitigation of Side Effects of Inhaled Corticosteroids.
abstract: Inhaled corticosteroids are used as one of the first-line drug therapy in patients with asthma. However, their long-term use is associated with various oropharyngeal and systemic side and adverse effects. Design of pro-soft drug is one of the strategies, which was adopted in the design of ciclesonide for mitigation of side effects usually observed with the use of inhaled corticosteroids. Ciclesonide, a pro-soft drug, is converted to an active metabolite desisobutyryl-ciclesonide in the lungs. The anti-inflammatory effect of desisobutyryl-ciclesonide is much higher than ciclesonide, and therefore, the local effect of the metabolite is higher with lower systemic side effects. Ciclesonide has favorable pharmacokinetic and pharmacodynamic properties as inhaled corticosteroid including low oral bioavailability, high plasma protein binding and rapid systemic clearance, high pulmonary deposition and distribution and long pulmonary residence duration. These advantageous properties make ciclesonide a very effective treatment option with low side effects. Various clinical studies support safety and efficacy of ciclesonide use in mild, moderate, and severe asthma patients.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610.
authors.forename: Jatinder Kaur
authors.initials: JK
authors.lastname: Mukker
authors.affiliation: Clinical Pharmacology and Pharmacometrics, AbbVie, North Chicago, Illinois 60064.
authors.forename: Ravi Shankar Prasad
authors.initials: RSP
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida 32610. Electronic address: hartmut@cop.ufl.edu.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000378:metabolism; D001682:Biological Availability; D015195:Drug Design; D006801:Humans; D008168:Lung / Q000378:metabolism; D011282:Pregnenediones / Q000009:adverse effects / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011485:Protein Binding; D014018:Tissue Distribution
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D011282:Pregnenediones; C494355:desisobutyrylciclesonide; C120481:ciclesonide
keywords: asthma; ciclesonide; desisobutyryl-ciclesonide; inhaled corticosteroids; pro-soft drug