CICLESONIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C32H44O7
Molecular Weight	540.6876
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[H][C@@]12C[C@H]3O[C@H](O[C@@]3(C(=O)COC(=O)C(C)C)[C@@]1(C)C[C@H](O)[C@@]4([H])[C@@]2([H])CCC5=CC(=O)C=C[C@]45C)C6CCCCC6

InChI

InChIKey=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

HIDE SMILES / InChI

Molecular Formula	C32H44O7
Molecular Weight	540.6876
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	8 / 9
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Ciclesonide is a glucocorticoid receptor agonist indicated for the treatment of allergic rhinitis (Omnaris nasal spray) and asthma (Alvesco). It was also developed by Byk Gulden for chronic obstructive pulmonary disease (COPD), but no development had been reported for this indication since 1999. Ciclesonide is a pro-drug and rapidly metabolized to C21-desisobutyryl-ciclesonide which is more potent toward GR receptor than the parent drug.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glucocorticoid receptor 172	Agonist 2,678

Conditions

Condition	Modality	Highest Phase	Product
Seasonal allergic rhinitis 64	Palliative	Approved 8,429	OMNARIS
Perennial allergic rhinitis 47	Palliative	Approved 8,429	OMNARIS
Asthma 241	Preventing	Approved 8,429	ALVESCO

C_max

Value	Dose	Analyte	Population
59.2 nM	0.64 mg single, intravenous	CICLESONIDE serum	Homo sapiens
4 ng/mL	400 μg single, respiratory	CICLESONIDE plasma	Homo sapiens
4.3 ng/mL	400 μg 1 times / day multiple, respiratory	CICLESONIDE plasma	Homo sapiens
15.2 ng/L	300 μg single, nasal	DES-CICLESONIDE serum	Homo sapiens
59.1 ng/L	300 μg single, nasal	DES-CICLESONIDE serum	Homo sapiens
586.2 ng/L	320 μg single, respiratory	DES-CICLESONIDE serum	Homo sapiens
35.3 ng/L	282 μg single, nasal	DES-CICLESONIDE serum	Homo sapiens
35.84 ng/L	282 μg 1 times / day multiple, nasal	DES-CICLESONIDE serum	Homo sapiens
0.31 ng/mL	400 μg single, respiratory	DES-CICLESONIDE plasma	Homo sapiens
0.41 ng/mL	400 μg 1 times / day multiple, respiratory	DES-CICLESONIDE plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
51 ng × min/mL	400 μg single, respiratory	CICLESONIDE plasma	Homo sapiens
62.3 ng × min/mL	400 μg 1 times / day multiple, respiratory	CICLESONIDE plasma	Homo sapiens
397.5 ng × h/L	300 μg single, nasal	DES-CICLESONIDE serum	Homo sapiens
2685 ng × h/L	320 μg single, respiratory	DES-CICLESONIDE serum	Homo sapiens
260 ng × h/L	282 μg single, nasal	DES-CICLESONIDE serum	Homo sapiens
337.8 ng × h/L	282 μg 1 times / day multiple, nasal	DES-CICLESONIDE serum	Homo sapiens
65.4 ng × min/mL	400 μg single, respiratory	DES-CICLESONIDE plasma	Homo sapiens
81.4 ng × min/mL	400 μg 1 times / day multiple, respiratory	DES-CICLESONIDE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
0.38 h	0.64 mg single, intravenous	CICLESONIDE serum	Homo sapiens
15 min	400 μg single, respiratory	CICLESONIDE plasma	Homo sapiens
13 min	400 μg 1 times / day multiple, respiratory	CICLESONIDE plasma	Homo sapiens
3.46 h	282 μg single, nasal	DES-CICLESONIDE serum	Homo sapiens
4.84 h	282 μg 1 times / day multiple, nasal	DES-CICLESONIDE serum	Homo sapiens
156 min	400 μg single, respiratory	DES-CICLESONIDE plasma	Homo sapiens
224 min	400 μg 1 times / day multiple, respiratory	DES-CICLESONIDE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
1%	800 μg single, intravenous		CICLESONIDE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
0.64 mg single, intravenous	healthy, 27.3 years (range: 19-40 years)
6.9 mg single, oral	healthy, 27.3 years (range: 19-40 years)
640 ug 2 times / day multiple, respiratory Highest studied dose	unhealthy, 48.3 years (range: 17-70 years)
10 mg single, oral Highest studied dose	healthy, adult
282 ug 1 times / day multiple, intranasal Highest studied dose	unhealthy, adult	Disc. AE: Burning sensation...

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AEs

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AE	Significance	Dose	Population
Burning sensation	severe, 1 patient Disc. AE	282 ug 1 times / day multiple, intranasal Highest studied dose	unhealthy, adult
Upper respiratory tract infection	below serious, 18 patients	100 ug 1 times / day steady, respiratory	unhealthy, children
Rhinitis	below serious, 4 patients	100 ug 1 times / day steady, respiratory	unhealthy, children
Ear infection	below serious, 5 patients	100 ug 1 times / day steady, respiratory	unhealthy, children
Pharyngitis	below serious, 5 patients	100 ug 1 times / day steady, respiratory	unhealthy, children

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737 inhibitor 1,587 inducer 781	inhibitor 1,767 inducer 389	substrate 1,217 inhibitor 1,852 inducer 97

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524 CYP2A6 707 CYP2C19 1,478 CYP2E1 882 P-gp 1,461 BCRP 699 CYP2B6 810 CYP2C8 911	CYP2C8 693 CYP4A11 119 P-gp 1,537	CYP1A2 701 CYP2A6 79 CYP2C19 293 CYP2E1 128 P-gp 257

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 1,692	inducer 1,573	no
CYP1A2 1,692	inhibitor 3,277	no
CYP2A6 739	inducer 1,573	no
CYP2A6 739	inhibitor 3,277	no
CYP2B6 1,001	inhibitor 3,277	no

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Drug as victim

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Target	Modality	Activity	Metabolite
P-gp 1,537	substrate 3,367	inconclusive
CYP2C8 693	substrate 3,367	minor
CYP2C8 693	substrate 3,367	yes	RM1 1
CYP2D6 1,217	substrate 3,367	yes
CYP2D6 1,217	substrate 3,367	yes	RM1 1

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
Achemtek	0104-021585	http://www.achemtek.com/126544-47-6
AHH Chemical co.,ltd	MT-49256	http://www.ahhchemical.com/product/MT-49256.html
AK Scientific, Inc. (AKSCI)	O945	http://www.aksci.com/item_detail.php?cat=O945
Alfa Chemistry	AP126544476	https://reagents.alfa-chemistry.com/product/ciclesonide-cas-126544-47-6-3410.html
Aurora Fine Chemicals LLC	A24.076.552	http://online.aurorafinechemicals.com/info?ID=A24.076.552

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PubMed

Show entries

Title	Date	PubMed
Gateways to clinical trials.	2004 Dec	15672123
Add-on therapy options in asthma not adequately controlled by inhaled corticosteroids: a comprehensive review.	2004 Oct 27	15509300
[Ciclesonide in the treatment of patients with bronchial asthma].	2005 Dec	16521412
Comparison of the oropharyngeal deposition of inhaled ciclesonide and fluticasone propionate in patients with asthma.	2005 Feb	15647406
Gateways to clinical trials.	2005 Jun	16082422

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Sample Use Guides

In Vivo Use Guide

Allergic rhinitis: The recommended dose of ciclesonide (in form of Omnaris Nasal Spray) is 200 ug per day administered as 2 sprays (50 mcg/spray) in each nostril once daily. Asthma: 80-320 ug twice daily.

Route of Administration: Other

In Vitro Use Guide

Ciclesonide at 10(-12)–10(-5) M signiﬁcantly inhibited TNF-alpha stimulated MCP-1 production in human airway smooth muscle cells. IL1-stimulated MCP-1 release was also signiﬁcantly inhibited in a concentration-dependent (10(-12)–10(-5) M) manner.