FLUNISOLIDE ANHYDROUS

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C24H31FO6
Molecular Weight	434.4987
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(C)O[C@]2([H])C[C@@]3([H])[C@]4([H])C[C@@]([H])(C5=CC(=O)C=C[C@]5(C)[C@@]4([H])[C@]([H])(C[C@]3(C)[C@]2(C(=O)CO)O1)O)F

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

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 167 Target ID: CHEMBL2034 Sources: http://www.drugbank.ca/drugs/DB00180	Agonist 2470
eosinophils 3 Target ID: CHEMBL614636 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9756205	Inhibitor 7728		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 8043	FLUNISOLIDE Approved Use Flunisolide Nasal Solution is indicated for the treatment of the nasal symptoms of seasonal or perennial rhinitis. Launch Date 1.0140768E12

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 1601

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1400

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1601	substrate 3113 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021247s000_ClinPharmR.pdf Page: 16.0	yes
P-gp 1400	substrate 3113 Sources: https://pubmed.ncbi.nlm.nih.gov/11724763/	yes

PubMed

Title	Date	PubMed
Poor sleep and daytime somnolence in allergic rhinitis: significance of nasal congestion.	2002	14720057
Flunisolide HFA.	2002	14720039
Inappropriate use of anti-asthmatic drugs in the Italian paediatric population.	2003 Oct	13680035
Effect of topical nasal corticosteroids on patients with chronic fatigue syndrome and rhinitis.	2003 Sep	14527077
Asthma steroid pharmacogenetics: a study strategy to identify replicated treatment responses.	2004	16113459
Safety and tolerability of treatments for allergic rhinitis in children.	2004	15366976
Hydrofluoroalkane formulations of inhaled corticosteroids for the treatment of asthma.	2004	15174892
Significant receptor affinities of metabolites and a degradation product of mometasone furoate.	2004 Jul 22	15285788
Add-on therapy options in asthma not adequately controlled by inhaled corticosteroids: a comprehensive review.	2004 Oct 27	15509300
Enhanced anti-inflammatory potency of a nitric oxide-releasing derivative of flunisolide: role of nuclear factor-kappaB.	2004 Sep	15128863
How do topical nasal corticosteroids improve sleep and daytime somnolence in allergic rhinitis?	2005 Dec	16337455
Effects of inhaled corticosteroids on bone.	2005 Jan	15702810
Comparison of the analysis of corticosteroids using different techniques.	2005 Jan	15700162
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
Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma.	2005 Jun 3	15935090
Evidence of remodeling in peripheral airways of patients with mild to moderate asthma: effect of hydrofluoroalkane-flunisolide.	2005 Nov	16275364
Use of Respimat Soft Mist inhaler in COPD patients.	2006	18046862
Pharmacological treatment of chronic obstructive pulmonary disease.	2006	18044097
Flunisolide decreases exhaled nitric oxide and nitrotyrosine levels in asthmatic children.	2006	17047290
Flunisolide attenuates nitric oxide-induced DNA damage in rat trachea epithelial cells.	2006	16696591
Efficacy of nebulized flunisolide combined with salbutamol and ipratropium bromide in stable patients with moderate-to-severe chronic obstructive pulmonary disease.	2006	16293958
Once-daily intranasal corticosteroids for allergic rhinitis. Examining Treatment issues.	2006 Apr	16972477
Meta-analysis finds use of inhaled corticosteroids during pregnancy safe: a systematic meta-analysis review.	2006 Aug	16937916
Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol.	2006 Jan 24	16433920
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
Effects of long-term inhaled corticosteroids on adrenal function in patients with asthma.	2006 Mar	16597078
Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells.	2006 Mar 17	16545134
Allergic rhinitis: evidence for impact on asthma.	2006 Nov 30	17140422
Topical glucocorticosteroids in rhinitis: clinical aspects.	2006 Oct	16923704
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
Hypertrichosis as a side effect of inhaled steroids in children.	2007 Apr	17351929
Topical nasal steroids for intermittent and persistent allergic rhinitis in children.	2007 Jan 24	17253485
Evidence-based selection of inhaled corticosteroid for treatment of chronic asthma.	2007 Jan-Feb	17365197
Human receptor kinetics and lung tissue retention of the enhanced-affinity glucocorticoid fluticasone furoate.	2007 Jul 25	17650349
Compressor/nebulizers differences in the nebulization of corticosteroids. The CODE study (Corticosteroids and Devices Efficiency).	2007 Jul-Aug	17876957
Montelukast in the management of allergic rhinitis.	2007 Jun	18360641
A reappraisal of the clinical efficacy of nebulized flunisolide in pediatric asthma: the Italian experience.	2007 Nov-Dec	17883883
Intranasal flunisolide treatment in children with adenoidal hypertrophy.	2007 Oct-Dec	18179756
Pharmacokinetics and tolerability (Study 1) with particular reference to ocular safety (Study 2) of tiotropium Respimat soft mist inhaler: findings from two dose-ranging studies in healthy men.	2008	18990967
New treatment options in allergic rhinitis: patient considerations and the role of ciclesonide.	2008 Apr	18728855
Relative oral corticosteroid-sparing effect of 7 inhaled corticosteroids in chronic asthma: a meta-analysis.	2008 Jul	18681088
Adrenal suppression and Cushing's syndrome secondary to an interaction between ritonavir and fluticasone: a review of the literature.	2008 Jul	18459946
The impact of generic-only drug benefits on patients' use of inhaled corticosteroids in a Medicare population with asthma.	2008 Jul 18	18638405
Nebulisation of corticosteroid suspensions and solutions with a beta(2) agonist.	2008 May	18416936
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies.	2008 Nov 4	18983670
Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications.	2008 Oct	18782107
Late development of esophageal stricture following radiation and chemotherapy for small cell carcinoma of the lung: A case report.	2008 Sep 19	18803839

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.

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