Through ester cleavage at the C21 position, the parent molecule ciclesonide is hydrolyzed to the active metabolite desisobutyryl ciclesonide (des-CIC), which subsequently reversibly produces fatty acid esters in lung cells. Normal human bronchial epithelial (NHBE) cells rapidly hydrolyze cleisonide (5 μM) (conversion rate around 30% at 4 hours), with nearly complete conversion at 24 hours [1].

Absorption, Distribution and Excretion
Ciclesonide and des-ciclesonide have negligible oral bioavailability (both less than 1%) due to low gastrointestinal absorption and high first-pass metabolism. The intranasal administration of ciclesonide at recommended doses results in negligible serum concentrations of ciclesonide.
152 L/hr [Following IV administration of 800 mcg of ciclesonide]

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Metabolism / Metabolites
Des-ciclesonide undergoes metabolism in the liver to additional metabolites mainly by the cytochrome P450 (CYP) 3A4 isozyme and to a lesser extent by CYP 2D6.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Although not measured, the amounts of inhaled corticosteroids absorbed into the maternal bloodstream and excreted into breastmilk are probably too small to affect a breastfed infant. Expert opinion considers inhaled, nasal and oral corticosteroids acceptable to use during breastfeeding.
◉ Effects in Breastfed Infants
None reported with any corticosteroid.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
The percentage of ciclesonide and des-ciclesonide bound to human plasma proteins averaged ≥ 99% each, with ≤ 1% of unbound drug detected in the systemic circulation.

[1]. The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol, 2007. 73(10): p. 1657-64.

Ciclesonide is an organic molecular entity.
Ciclesonide is a glucocorticoid used to treat obstructive airway diseases. It is marketed under the brand name Alvesco.
Ciclesonide is a nonhalogenated, synthetic, inhaled corticosteroid (ICS) with anti-inflammatory and potential antiviral activities. Upon administration by oral inhalation into the lungs, ciclesonide (CIC) is converted by local esterases to its active metabolite desisobutyryl-ciclesonide (des-CIC), which binds to intracellular glucocorticoid receptors (GRs). The ligand-bound GRs regulate gene expressions, which lead to inhibitory activities against multiple cell types, such as mast cells, eosinophils, basophils, lymphocytes, macrophages and neutrophils, and various mediators associated with inflammation, such as histamine, eicosanoids, leukotrienes and cytokines. In addition, ciclesonide may suppress the replication of human coronavirus by targeting viral nonstructural protein 15 (NSP15).

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Drug Indication
For the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older.
For the alleviation of clinical signs of severe equine asthma (formerly known as Recurrent Airway Obstruction – (RAO), Summer Pasture Associated Recurrent Airway Obstruction – (SPA-RAO)).

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Mechanism of Action
Glucocorticoids such as ciclesonide can inhibit leukocyte infiltration at the site of inflammation, interfere with mediators of inflammatory response, and suppress humoral immune responses. The antiinflammatory actions of glucocorticoids are thought to involve phospholipase A2 inhibitory proteins, lipocortins, which control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes. Ciclesonide reduces inflammatory reaction by limiting the capillary dilatation and permeability of the vascular structures. These compounds restrict the accumulation of polymorphonuclear leukocytes and macrophages and reduce the release of vasoactive kinins. Recent research suggests that corticosteroids may inhibit the release of arachidonic acid from phospholipids, thereby reducing the formation of prostaglandins. Ciclesonide is a glucocorticoid receptor agonist. On binding, the corticoreceptor-ligand complex translocates itself into the cell nucleus, where it binds to many glucocorticoid response elements (GRE) in the promoter region of the target genes. The DNA bound receptor then interacts with basic transcription factors, causing an increase or decrease in expression of specific target genes, including suppression of IL2 (interleukin 2) expression.

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Pharmacodynamics
Ciclesonide is a pro-drug that is enzymatically hydrolyzed to a pharmacologically active metabolite, C21-desisobutyryl-ciclesonide (des-ciclesonide or RM1) following intranasal application. Des-ciclesonide has anti-inflammatory activity with affinity for the glucocorticoid receptor that is 120 times higher than the parent compound. The precise mechanism through which ciclesonide affects allergic rhinitis symptoms is not known. Corticosteroids have been shown to have a wide range of effects on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic inflammation.

C32H44O7

540.6876

540.309

126544-47-6

Desisobutyryl-ciclesonide;161115-59-9;Ciclesonide (Standard);126544-47-6;Ciclesonide-d7;1225382-70-6

6918155

White to off-white solid powder

1.23 g/cm3

665ºC at 760 mmHg

202-209?C

210ºC

1.61E-20mmHg at 25°C

1.575

4.703

1

7

6

39

1100

9

O1[C@]([H])(C2([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C2([H])[H])O[C@]2([H])C([H])([H])[C@@]3([H])[C@]4([H])C([H])([H])C([H])([H])C5=C([H])C(C([H])=C([H])[C@]5(C([H])([H])[H])[C@@]4([H])[C@]([H])(C([H])([H])[C@]3(C([H])([H])[H])[C@]12C(C([H])([H])OC(C([H])(C([H])([H])[H])C([H])([H])[H])=O)=O)O[H])=O

LUKZNWIVRBCLON-GXOBDPJESA-N

InChI=1S/C32H44O7/c1-18(2)28(36)37-17-25(35)32-26(38-29(39-32)19-8-6-5-7-9-19)15-23-22-11-10-20-14-21(33)12-13-30(20,3)27(22)24(34)16-31(23,32)4/h12-14,18-19,22-24,26-27,29,34H,5-11,15-17H2,1-4H3/t22-,23-,24-,26+,27+,29+,30-,31-,32+/m0/s1

[2-[(1S,2S,4R,6R,8S,9S,11S,12S,13R)-6-cyclohexyl-11-hydroxy-9,13-dimethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-8-yl]-2-oxoethyl] 2-methylpropanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~50 mg/mL (~92.47 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.62 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.62 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)