FLUNISOLIDE ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H31FO6
Molecular Weight	434.4977
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12C[C@@]3([H])[C@]4([H])C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@@H](O)C[C@]3(C)[C@@]1(OC(C)(C)O2)C(=O)CO

InChI

InChIKey=XSFJVAJPIHIPKU-XWCQMRHXSA-N

InChI=1S/C24H31FO6/c1-21(2)30-19-9-14-13-8-16(25)15-7-12(27)5-6-22(15,3)20(13)17(28)10-23(14,4)24(19,31-21)18(29)11-26/h5-7,13-14,16-17,19-20,26,28H,8-11H2,1-4H3/t13-,14-,16-,17-,19+,20+,22-,23-,24+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C24H31FO6
Molecular Weight	434.4977
Charge	0
Count

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

Description
Sources: http://www.drugbank.ca/drugs/DB00180
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/flunisolide.html

Flunisolide is a synthetic corticosteroid. It is administered either as an oral metered-dose inhaler for the treatment of asthma or as a nasal spray for treating allergic rhinitis. Corticosteroids are naturally occurring hormones that prevent or suppress inflammation and immune responses. When given as an intranasal spray, flunisolide reduces watery nasal discharge (rhinorrhea), nasal congestion, postnasal drip, sneezing, and itching oat the back of the throat that are common allergic symptoms. Flunisolide is a glucocorticoid receptor agonist. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flunisolide binds to plasma transcortin, and it becomes active when it is not bound to transcortin. It is used for the maintenance treatment of asthma as a prophylactic therapy. Flunisolide is marketed as AeroBid, Nasalide, Nasarel.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: http://www.drugbank.ca/drugs/DB00180	Agonist 2678
eosinophils 3 Target ID: CHEMBL614636 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9756205	Inhibitor 8297		32.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Perennial or seasonal allergic rhinitis 6 Sources: https://www.drugs.com/pro/flunisolide.html	Primary		Approved 8429	FLUNISOLIDE Approved Use Flunisolide Nasal Solution is indicated for the treatment of the nasal symptoms of seasonal or perennial rhinitis. Launch Date 2002

C_max

Value	Dose	Co-administered	Analyte	Population
1 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021247s008lbl.pdf	160 μg 2 times / day multiple, respiratory dose: 160 μg route of administration: Respiratory experiment type: MULTIPLE co-administered:		FLUNISOLIDE unknown	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1.2 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021247s008lbl.pdf	160 μg 2 times / day multiple, respiratory dose: 160 μg route of administration: Respiratory experiment type: MULTIPLE co-administered:		FLUNISOLIDE unknown	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.7 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9505980	0.5 mg single, respiratory dose: 0.5 mg route of administration: Respiratory experiment type: SINGLE co-administered:		FLUNISOLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
20% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/9505980	0.5 mg single, respiratory dose: 0.5 mg route of administration: Respiratory experiment type: SINGLE co-administered:		FLUNISOLIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
160 ug 2 times / day steady, respiratory (starting) Recommended Dose: 160 ug, 2 times / day Route: respiratory Route: steady Dose: 160 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf	unhealthy, 4-78 years n = 217 Health Status: unhealthy Condition: asthma Age Group: 4-78 years Sex: M+F Population Size: 217 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf	Other AEs: Headache, Fever... Other AEs: Headache (13.8%) Fever (3.7%) Allergic reaction (4.6%) Pain (4.6%) Accidental injury (3.7%) Infection (0.9%) Back pain (3.2%) Vomiting (4.6%) Dyspepsia (3.2%) Pharyngitis (16.6%) Rhinitis (15.7%) Cough increased (5.5%) Sinusitis (4.1%) Epistaxis (0.9%) Rash (3.7%) Urinary tract infection (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf
320 ug 2 times / day steady, respiratory (starting) Recommended Dose: 320 ug, 2 times / day Route: respiratory Route: steady Dose: 320 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf	unhealthy, 4-78 years n = 113 Health Status: unhealthy Condition: asthma Age Group: 4-78 years Sex: M+F Population Size: 113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf	Other AEs: Headache, Fever... Other AEs: Headache (8.8%) Fever (0.9%) Allergic reaction (4.4%) Pain (1.8%) Accidental injury (3.5%) Infection (0.9%) Back pain (1.8%) Dyspepsia (3.5%) Pharyngitis (16.8%) Rhinitis (3.5%) Cough increased (1.8%) Sinusitis (8.8%) Rash (1.8%) Urinary tract infection (3.5%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf
80 ug 2 times / day steady, respiratory (starting) Recommended Dose: 80 ug, 2 times / day Route: respiratory Route: steady Dose: 80 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf	unhealthy, 4-78 years n = 189 Health Status: unhealthy Condition: asthma Age Group: 4-78 years Sex: M+F Population Size: 189 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf	Other AEs: Headache, Fever... Other AEs: Headache (9%) Fever (6.9%) Allergic reaction (4.2%) Pain (2.6%) Accidental injury (3.7%) Infection (3.7%) Back pain (0.5%) Vomiting (4.2%) Dyspepsia (2.1%) Pharyngitis (17.5%) Rhinitis (9%) Cough increased (8.5%) Sinusitis (7.4%) Epistaxis (3.2%) Rash (2.6%) Urinary tract infection (1.1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021247LBL.pdf
85 ug 2 times / day steady, respiratory Dose: 85 ug, 2 times / day Route: respiratory Route: steady Dose: 85 ug, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021247s000_ClinPharmR.pdf	unhealthy, 6-11 years n = 510 Health Status: unhealthy Condition: asthma Age Group: 6-11 years Population Size: 510 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021247s000_ClinPharmR.pdf	Disc. AE: Asthma, Pharyngitis... AEs leading to discontinuation/dose reduction: Asthma (10%) Pharyngitis (1.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021247s000_ClinPharmR.pdf

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021247s000_ClinPharmR.pdf Page: 16.0	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11724763/	yes

PubMed

Title	Date	PubMed
Topical corticosteroids in nasal polyposis.	2001	11368283
Flunisolide HFA vs flunisolide CFC: pharmacokinetic comparison in healthy volunteers.	2001 Dec	11870676
Aerosol characterization of nebulized intranasal glucocorticoid formulations.	2001 Summer	11681655
Metering performance of several metered-dose inhalers with different spacers/holding chambers.	2001 Winter	11791683
Poor sleep and daytime somnolence in allergic rhinitis: significance of nasal congestion.	2002	14720057
Flunisolide HFA.	2002	14720039
Nasal cellularity in 183 unselected schoolchildren aged 9 to 11 years.	2002 Dec	12456911
Systemic effect comparisons of six inhaled corticosteroid preparations.	2002 May 15	12016099
Intranasal corticosteroids versus topical H1 receptor antagonists for the treatment of allergic rhinitis: a systematic review with meta-analysis.	2002 Nov	12452206
Evaluation of efficacy and safety of flunisolide hydrofluoroalkane for the treatment of asthma.	2003 Mar	12852702
Inappropriate use of anti-asthmatic drugs in the Italian paediatric population.	2003 Oct	13680035
A randomized controlled trial of inhaled flunisolide in the management of acute asthma in children.	2003 Sep	12969999
Asthma steroid pharmacogenetics: a study strategy to identify replicated treatment responses.	2004	16113459
Evaluation of the utilization patterns of leukotriene modifiers in a large managed care health plan.	2004 Mar-Apr	15032560
Treatment with inhaled flunisolide.	2004 May	15136418
[Hydrofluoroalkane as a propellant for pressurized metered-dose inhalers: history, pulmonary deposition, pharmacokinetics, efficacy and safety].	2004 Nov-Dec	15622419
Effects of drug treatment on inflammation and hyperreactivity of airways and on immune variables in cats with experimentally induced asthma.	2005 Jul	16111148
The nitrosterols--a step forward from the steroid anti-inflammatory drugs?	2005 Jul	16022571
Evidence of remodeling in peripheral airways of patients with mild to moderate asthma: effect of hydrofluoroalkane-flunisolide.	2005 Nov	16275364
Pharmacological treatment of chronic obstructive pulmonary disease.	2006	18044097
Inhaled flunisolide suppresses the hypothalamic-pituitary-adrenocortical axis, but has minimal systemic immune effects in healthy cats.	2006 Jan-Feb	16496924
Ciclesonide for the treatment of asthma.	2006 Mar	18360579
Nebulized drug admixtures: effect on aerosol characteristics and albuterol output.	2006 Winter	17196077
A dose-ranging study of tiotropium delivered via Respimat Soft Mist Inhaler or HandiHaler in COPD patients.	2007	18268929
Compressor/nebulizers differences in the nebulization of corticosteroids. The CODE study (Corticosteroids and Devices Efficiency).	2007 Jul-Aug	17876957
A reappraisal of the clinical efficacy of nebulized flunisolide in pediatric asthma: the Italian experience.	2007 Nov-Dec	17883883
New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide.	2008 Apr	18728855

Patents

Sample Use Guides

In Vivo Use Guide

Initial dose: 2 sprays in each nostril 2 times a day. If needed, this dose may be increased to 2 sprays in each nostril 3 times a day. Maximum total daily doses should not exceed 8 sprays in each nostril.

Route of Administration: Nasal

In Vitro Use Guide

Flunisolide at all the tested concentrations ((0.1 to 10 uM) effectively inhibited ICAM-1 expression and GM-CSF and IL-5 release. The percent inhibition induced by the highest flunisolide concentration (10 uM) for the various BEAS-2B functions was 30%, 60%, and 70%, respectively.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:47:17 GMT 2023` Edited by `admin` on `Fri Dec 15 17:47:17 GMT 2023`
Record UNII	78M02AA8KF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FLUNISOLIDE ANHYDROUS

Common Name

English

FLUNISOLIDE [MI]

Common Name

English

6.ALPHA.-FLUORO-11.BETA.,16.ALPHA.,17,21-TETRAHYDROXYPREGNA-1,4-DIENE-3,20-DIONE CYCLIC 16,17-ACETAL WITH ACETONE

Common Name

English

flunisolide [INN]

Common Name

English

PREGNA-1,4-DIENE-3,20-DIONE, 6-FLUORO-11,21-DIHYDROXY-16,17-((1-METHYLETHYLIDENE)BIS(OXY))- (6.ALPHA.,11.BETA.,16.ALPHA.)-

Common Name

English

Flunisolide [WHO-DD]

Common Name

English

Classification Tree Code System Code

WHO-ATC

R03BA03