Identification

Name
Ciclesonide
Accession Number
DB01410
Type
Small Molecule
Groups
Approved, Investigational
Description

Ciclesonide is a glucocorticoid used to treat obstructive airway diseases. It is marketed under the brand name Alvesco.

Structure
Thumb
Synonyms
  • Ciclesonida
  • Ciclesonide
External IDs
BI54903 / RPR-251526 / RPR251526
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AlvescoAerosol, metered80 ug/1Respiratory (inhalation)Covis Pharma2018-03-26Not applicableUs
AlvescoAerosol, metered160 ug/1Respiratory (inhalation)Sunovion2008-10-01Not applicableUs
AlvescoAerosol, metered100 mcgRespiratory (inhalation)Astra Zeneca2006-09-27Not applicableCanada
AlvescoAerosol, metered80 ug/1Respiratory (inhalation)Physicians Total Care, Inc.2009-02-19Not applicableUs
AlvescoAerosol, metered80 ug/1Respiratory (inhalation)Sunovion2008-10-01Not applicableUs
AlvescoAerosol, metered50 mcgRespiratory (inhalation)TakedaNot applicableNot applicableCanada
AlvescoAerosol, metered160 ug/1Respiratory (inhalation)Covis Pharma2018-03-26Not applicableUs
AlvescoAerosol, metered200 mcgRespiratory (inhalation)Astra Zeneca2006-09-27Not applicableCanada
AlvescoAerosol, metered160 ug/1Respiratory (inhalation)Physicians Total Care, Inc.2009-02-23Not applicableUs
OmnarisSpray, metered50 mcgNasalAstra Zeneca2008-04-10Not applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-ciclesonideSpray, metered50 mcgNasalApotex Corporation2016-11-25Not applicableCanada
International/Other Brands
Omniair
Categories
UNII
S59502J185
CAS number
126544-47-6
Weight
Average: 540.697
Monoisotopic: 540.308703757
Chemical Formula
C32H44O7
InChI Key
LUKZNWIVRBCLON-GXOBDPJESA-N
InChI
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
IUPAC Name
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
SMILES
[H][C@@]12C[C@@]3([H])[C@]4([H])CCC5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@H](O)C[C@]3(C)[C@@]1(O[C@@H](O2)C1CCCCC1)C(=O)COC(=O)C(C)C

Pharmacology

Indication

For the treatment of nasal symptoms associated with seasonal and perennial allergic rhinitis in adults and adolescents 12 years of age and older.

Associated Conditions
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.

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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption

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.

Volume of distribution
Not Available
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.

Metabolism

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.

Route of elimination
Not Available
Half life
Not Available
Clearance
  • 152 L/hr [Following IV administration of 800 mcg of ciclesonide]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Ciclesonide.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Ciclesonide.
1-TestosteroneThe risk or severity of edema formation can be increased when 1-Testosterone is combined with Ciclesonide.
1,10-PhenanthrolineThe therapeutic efficacy of 1,10-Phenanthroline can be decreased when used in combination with Ciclesonide.
16-BromoepiandrosteroneThe risk or severity of edema formation can be increased when 16-Bromoepiandrosterone is combined with Ciclesonide.
19-norandrostenedioneThe risk or severity of edema formation can be increased when 19-norandrostenedione is combined with Ciclesonide.
1alpha-Hydroxyvitamin D5The therapeutic efficacy of 1alpha-Hydroxyvitamin D5 can be decreased when used in combination with Ciclesonide.
2-MethoxyethanolThe risk or severity of adverse effects can be increased when Ciclesonide is combined with 2-Methoxyethanol.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Ciclesonide.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Ciclesonide.
Food Interactions
Not Available

References

Synthesis Reference

Beate Schmidt, "Process for preparing crystalline ciclesonide with defined particle size." U.S. Patent US20060128954, issued June 15, 2006.

US20060128954
General References
  1. Mutch E, Nave R, McCracken N, Zech K, Williams FM: The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol. 2007 May 15;73(10):1657-64. Epub 2007 Jan 28. [PubMed:17331475]
External Links
KEGG Drug
D01703
PubChem Compound
6918155
PubChem Substance
46508553
ChemSpider
5293368
ChEBI
31397
ChEMBL
CHEMBL2040682
Therapeutic Targets Database
DAP000423
PharmGKB
PA164781399
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Ciclesonide
ATC Codes
R03BA08 — CiclesonideR01AD13 — Ciclesonide
AHFS Codes
  • 68:04.00 — Adrenals
  • 52:08.08 — Corticosteroids

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
2CompletedTreatmentPulmonary Disease, Chronic Obstructive1
2Unknown StatusTreatmentAsthma Bronchial1
2WithdrawnTreatmentAsthma Bronchial1
3CompletedNot AvailableAsthma Bronchial1
3CompletedPreventionAllergic Rhinitis (AR) / Perennial Allergic Rhinitis (PAR) / Pollen Allergy1
3CompletedPreventionAsthma Bronchial1
3CompletedTreatmentAllergic Rhinitis (AR) / Perennial Allergic Rhinitis (PAR) / Pollen Allergy2
3CompletedTreatmentAsthma Bronchial21
3CompletedTreatmentAsthma Bronchial / Respiratory Hypersensitivity / Respiratory Tract Diseases1
3CompletedTreatmentBronchial Asthma1
3CompletedTreatmentPerennial Allergic Rhinitis (PAR)3
3CompletedTreatmentPerennial Allergic Rhinitis (PAR) / Pollen Allergy1
3CompletedTreatmentPollen Allergy / Rhinitis, Allergic, Perennial1
3CompletedTreatmentPollen Allergy / Rhinitis, Allergic, Seasonal3
3CompletedTreatmentRhinitis, Allergic, Perennial2
3CompletedTreatmentSeasonal Allergic Rhinitis (SAR)2
3Not Yet RecruitingTreatmentChronic Rhinosinustis With Polyps1
4CompletedTreatmentAllergic Rhinitis (AR)2
4CompletedTreatmentAllergic Rhinitis (AR) / Asthma Bronchial1
4CompletedTreatmentAsthma Bronchial4
4CompletedTreatmentPerennial Allergic Rhinitis (PAR)1
Not AvailableCompletedNot AvailableAllergies / Asthma Bronchial1
Not AvailableCompletedNot AvailableAsthma Bronchial1
Not AvailableCompletedTreatmentAsthma Bronchial1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • 3M Health Care
  • Nycomed Inc.
  • Physicians Total Care Inc.
  • Sepracor Pharmaceuticals Inc.
Dosage forms
FormRouteStrength
Aerosol, meteredRespiratory (inhalation)100 mcg
Aerosol, meteredRespiratory (inhalation)160 ug/1
Aerosol, meteredRespiratory (inhalation)200 mcg
Aerosol, meteredRespiratory (inhalation)50 mcg
Aerosol, meteredRespiratory (inhalation)80 ug/1
SprayNasal50 ug/1
Spray, meteredNasal50 mcg
Aerosol, meteredNasal50 mcg
Aerosol, meteredNasal37 ug/1
Prices
Unit descriptionCostUnit
Alvesco 160 mcg/act Aerosol 6.1 gm Inhaler162.24USD inhaler
Alvesco 80 mcg/act Aerosol 6.1 gm Inhaler162.24USD inhaler
Alvesco 160 mcg inhaler31.1USD g
Alvesco 80 mcg inhaler31.1USD g
Omnaris 50 mcg nasal spray11.01USD g
Alvesco 200 mcg/dose Metered Dose Aerosol0.66USD dose
Alvesco 100 mcg/dose Metered Dose Aerosol0.4USD dose
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5695743No1997-12-092010-07-06Us
CA2388325No2007-09-182020-10-20Canada
CA2050812No2003-07-292011-09-06Canada
US5775321No1998-07-072015-07-07Us
US5482934No1996-01-092017-10-24Us
US8371292No2013-02-122028-02-01Us
US7235247No2007-06-262019-04-21Us
US6767901No2004-07-272020-10-21Us
US6939559No2005-09-062019-04-21Us
US8383611No2013-02-262020-10-20Us
US6264923No2001-07-242018-05-13Us
US6006745No1999-12-282016-12-28Us
US6120752No2000-09-192018-05-13Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00157 mg/mLALOGPS
logP4.08ALOGPS
logP5.32ChemAxon
logS-5.5ALOGPS
pKa (Strongest Acidic)14.78ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area99.13 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity146.28 m3·mol-1ChemAxon
Polarizability60.18 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9907
Blood Brain Barrier+0.9439
Caco-2 permeable-0.6847
P-glycoprotein substrateSubstrate0.7787
P-glycoprotein inhibitor IInhibitor0.8247
P-glycoprotein inhibitor IIInhibitor0.9476
Renal organic cation transporterNon-inhibitor0.7744
CYP450 2C9 substrateNon-substrate0.8232
CYP450 2D6 substrateNon-substrate0.915
CYP450 3A4 substrateSubstrate0.774
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.7104
CYP450 2D6 inhibitorNon-inhibitor0.9407
CYP450 2C19 inhibitorNon-inhibitor0.9151
CYP450 3A4 inhibitorNon-inhibitor0.6192
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8478
Ames testNon AMES toxic0.9032
CarcinogenicityNon-carcinogens0.9367
BiodegradationNot ready biodegradable0.9897
Rat acute toxicity3.5547 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9738
hERG inhibition (predictor II)Non-inhibitor0.595
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as gluco/mineralocorticoids, progestogins and derivatives. These are steroids with a structure based on a hydroxylated prostane moiety.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Pregnane steroids
Direct Parent
Gluco/mineralocorticoids, progestogins and derivatives
Alternative Parents
20-oxosteroids / 3-oxo delta-1,4-steroids / 11-beta-hydroxysteroids / Delta-1,4-steroids / Alpha-acyloxy ketones / 1,3-dioxolanes / Secondary alcohols / Cyclic ketones / Cyclic alcohols and derivatives / Carboxylic acid esters
show 5 more
Substituents
Progestogin-skeleton / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 11-hydroxysteroid / 11-beta-hydroxysteroid / Oxosteroid / Hydroxysteroid / Delta-1,4-steroid / Alpha-acyloxy ketone
show 18 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
References
  1. Barnes NC: The properties of inhaled corticosteroids: similarities and differences. Prim Care Respir J. 2007 Jun;16(3):149-54. [PubMed:17530144]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Peet CF, Enos T, Nave R, Zech K, Hall M: Identification of enzymes involved in phase I metabolism of ciclesonide by human liver microsomes. Eur J Drug Metab Pharmacokinet. 2005 Oct-Dec;30(4):275-86. [PubMed:16435573]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Mutch E, Nave R, McCracken N, Zech K, Williams FM: The role of esterases in the metabolism of ciclesonide to desisobutyryl-ciclesonide in human tissue. Biochem Pharmacol. 2007 May 15;73(10):1657-64. Epub 2007 Jan 28. [PubMed:17331475]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Steroid binding
Specific Function
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
Gene Name
SERPINA6
Uniprot ID
P08185
Uniprot Name
Corticosteroid-binding globulin
Molecular Weight
45140.49 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on July 17, 2007 06:38 / Updated on December 18, 2018 05:46