Dose-dependent effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic rhinitis (SAR)*1

Ratner, Paul H.; Bavel, Julius H. van; Hampel, Frank C.; Wingertzahn, Mark A.; Darken, Patrick; Shah, Tushar; Hellbardt, S.; Brookman, Sheldon

doi:10.1016/j.jaci.2003.12.055

Cited by 8 publications

(3 citation statements)

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“…Excellent tolerance at both local and systemic levels was seen (Meltzer and Derendorf 2006). These data confi rmed the results of previous clinical trials (Ratner et al 2004;Nave et al 2006;Meltzer et al 2007).…”

Section: Effi Cacy and Safety Of Ciclesonidesupporting

confidence: 88%

New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide

Braido

Lagasio²,

Piroddi³

et al. 2008

TCRM

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Allergic rhinitis (AR) is a chronic infl ammatory respiratory disease affecting 5%-50% of the worldwide population and its prevalence is increasing (Herman 2007). In addition, AR is associated with asthma and other co-morbidities such as conjunctivitis and sinusitis. The main symptoms are nasal congestion, rhinorrea, sneezing, itching, and post-nasal drainage induced after allergen exposure by an IgE-mediated infl ammation of the membranes lining the nose. AR is not a life-threatening disease, but it has been shown to have a signifi cant impact on quality of life. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines propose a classifi cation of AR in intermittent and persistent, each graded as mild or moderate-severe, and provide a stepwise approach to the treatment. Inhaled steroids and antihistamine are the main tools in AR therapy but more safe and effective drugs are, however, needed. Inhaled steroid ciclesonide appears to be safe and effective.

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Section: Effi Cacy and Safety Of Ciclesonidesupporting

confidence: 88%

New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide

Braido

Lagasio²,

Piroddi³

et al. 2008

TCRM

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“…Retention on the nasal epithelium allows ciclesonide to provide sustained anti-inflammatory activity and, thereby, supports once-daily dosing with a 24 h effect. Intranasal ciclesonide 200 mg was superior to placebo in relieving nasal symptoms in adult and adolescent patients with seasonal AR when administered as a once-daily dose [22]. Although ciclesonide was administered once daily in the morning, the signs and symptoms of AR were adequately controlled throughout the intervening 24 h period.…”

Section: Discussionmentioning

confidence: 96%

In vitro metabolism of ciclesonide in human nasal epithelial cells

Sato

Nave²,

Nonaka

et al. 2006

Biopharm & Drug Disp

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Ciclesonide, a corticosteroid in development for allergic rhinitis, is converted to the pharmacologically active metabolite, desisobutyryl-ciclesonide (des-CIC), and des-CIC is subsequently esterified with fatty acids. Various experiments were performed to investigate ciclesonide metabolism in human nasal epithelial cells (HNEC). Human nasal epithelial cells were incubated with (a) 0.1 microM ciclesonide for 1 h and medium without ciclesonide for up to 24 h, (b) esterase inhibitors for 0.5 h followed by 5 microM ciclesonide for 6 h, or (c) 1 microM des-CIC for 6 h followed by medium without des-CIC for up to 24 h. Ciclesonide, des-CIC and des-CIC fatty acid conjugate concentrations were determined by high-performance liquid chromatography with tandem mass spectrometry. The amount of ciclesonide in HNEC decreased approximately 93-fold from 0.5 to 24 h. In contrast, des-CIC was present at constant levels throughout the post-treatment period. Furthermore, fatty acid conjugates of des-CIC were retained in HNEC up to 24 h post-treatment. Carboxylesterase and cholinesterase inhibitors decreased ciclesonide metabolism > or =50%. The total amounts of des-CIC fatty acid conjugates decreased and the extracellular amounts of des-CIC increased with time. In conclusion, ciclesonide was rapidly converted to des-CIC by carboxylesterases and cholinesterases, and des-CIC underwent reversible fatty acid conjugation in HNEC.

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“…These data along with the conservation of the metabolic enzymes involved in ciclesonide hydrolysis to des-CIC among mammalian species indicate that ciclesonide is likely to be converted to the pharmacologically active metabolite, des-CIC, in human nasal mucosa. The recent report that intranasal administration of ciclesonide 200 mg once daily provided effective symptom relief in patients with AR [21] suggests that ciclesonide is converted to des-CIC in human nasal mucosa. The presence of active metabolite in the nasal mucosa supports the continued clinical development of ciclesonide for the treatment of AR.…”

Section: Discussionmentioning

confidence: 99%

In vitro activation of the corticosteroid ciclesonide in animal nasal mucosal homogenates

Sato

Nave²,

Nonaka

et al. 2007

Biopharm & Drug Disp

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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.

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Dose-dependent effectiveness of ciclesonide nasal spray in the treatment of seasonal allergic rhinitis (SAR)*1

Cited by 8 publications

References 0 publications

New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide

New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide

In vitro metabolism of ciclesonide in human nasal epithelial cells

In vitro activation of the corticosteroid ciclesonide in animal nasal mucosal homogenates

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