Identification

Name
Flunisolide
Accession Number
DB00180  (APRD00976)
Type
Small Molecule
Groups
Approved, Investigational
Description

Flunisolide (marketed as AeroBid, Nasalide, Nasarel) is a corticosteroid often prescribed as treatment for allergic rhinitis. The principle mechanism of action of flunisolide is to activate glucocorticoid receptors. It also has anti-inflammatory action.

Structure
Thumb
Synonyms
  • Flunisolida
  • Flunisolide
  • Flunisolide anhydrous
  • Flunisolidum
Product Ingredients
IngredientUNIICASInChI Key
Flunisolide hemihydrateQK4DYS664X77326-96-6MIXMJCQRHVAJIO-TZHJZOAOSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AerobidAerosol, metered250 ug/1Respiratory (inhalation)Forest Laboratories2005-03-022012-03-21Us
Aerobid-MAerosol, metered250 ug/1Respiratory (inhalation)Forest Laboratories2005-03-022011-06-30Us
AerospanAerosol, metered80 ug/1Respiratory (inhalation)FOREST PHARMACEUTICALS, INC.2007-05-28Not applicableUs
AerospanAerosol, metered80 ug/1Respiratory (inhalation)Meda Pharmaceuticals Ltd2012-03-01Not applicableUs
AerospanAerosol, metered80 ug/1Respiratory (inhalation)Acton Pharmaceuticals, Inc.2012-03-012017-12-31Us
Bronalide Inhal 250mcg/aemAerosol, metered250 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee1988-12-311999-02-15Canada
NasarelSolution29 ug/1NasalTeva Respiratory LLC1995-09-102009-12-31Us
RhinalarSpray.025 %NasalSyntex Inc.1978-12-311996-09-30Canada
Rhinalar Nasal MistSolution; Spray25 mcgNasalIvax Pharmaceuticals Incorporated1996-12-312015-10-26Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-flunisolide Nasal Spray0.25 mgNasalApotex Corporation2000-03-10Not applicableCanada
FlunisolideSolution0.25 mg/1mLNasalRemedy Repack2016-02-172017-02-23Us
FlunisolideSpray, metered0.25 mg/1mLNasalRising Pharmaceuticals2006-08-03Not applicableUs
FlunisolideSolution0.25 mg/1mLNasalRemedy Repack2017-08-18Not applicableUs
FlunisolideSpray, metered0.25 mg/1mLNasalRising Pharmaceuticals2006-11-282014-11-19Us
FlunisolideSolution0.25 mg/1mLNasalPhysicians Total Care, Inc.2003-05-23Not applicableUs
FlunisolideSolution0.25 mg/1mLNasalBauch & Lomb Incorporated2002-02-20Not applicableUs
FlunisolideSpray, metered29 ug/1NasalApotex Corporation2007-08-102011-07-30Us
Novo-flunisolideSpray25 mcgNasalNovopharm Limited1998-06-302005-08-10Canada
PMS-flunisolideSpray0.025 %NasalPharmascience Inc1994-12-312009-08-27Canada
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AerobidFlunisolide hemihydrate (250 ug/1)Aerosol, meteredRespiratory (inhalation)Physicians Total Care, Inc.1995-11-292011-05-31Us
AerobidFlunisolide hemihydrate (250 ug/1)Aerosol, meteredRespiratory (inhalation)Physicians Total Care, Inc.2005-05-162011-06-30Us
International/Other Brands
AeroBid (Roche) / Bronalide (Krewel) / Nasalide (Teva Santé) / Nasarel / Syntaris (Teva)
Categories
UNII
78M02AA8KF
CAS number
3385-03-3
Weight
Average: 434.4977
Monoisotopic: 434.210466929
Chemical Formula
C24H31FO6
InChI Key
XSFJVAJPIHIPKU-XWCQMRHXSA-N
InChI
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
IUPAC Name
(1S,2S,4R,8S,9S,11S,12S,13R,19S)-19-fluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.0²,⁹.0⁴,⁸.0¹³,¹⁸]icosa-14,17-dien-16-one
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

Pharmacology

Indication

For the maintenance treatment of asthma as a prophylactic therapy.

Associated Conditions
Pharmacodynamics

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.

Mechanism of action

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.

TargetActionsOrganism
AGlucocorticoid receptor
agonist
Human
Absorption

Absorbed rapidly

Volume of distribution
Not Available
Protein binding

Approximately 40% after oral inhalation

Metabolism

Primarily hepatic, converted to the S beta-OH metabolite.

Route of elimination
Not Available
Half life

1.8 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

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

References

Synthesis Reference

Richard E. Jones, Jacquelyn A. Smithers, "Process for preparing flunisolide." U.S. Patent US4273710, issued July, 1965.

US4273710
General References
Not Available
External Links
Human Metabolome Database
HMDB0014326
KEGG Compound
C07005
PubChem Compound
82153
PubChem Substance
46507894
ChemSpider
74144
ChEBI
5106
ChEMBL
CHEMBL1512
Therapeutic Targets Database
DAP001046
PharmGKB
PA449661
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Flunisolide
ATC Codes
R01AD04 — FlunisolideR03BA03 — Flunisolide
AHFS Codes
  • 68:04.00 — Adrenals
  • 52:08.00 — Anti-inflammatory Agents
  • 52:08.08 — Corticosteroids
FDA label
Download (4.31 MB)
MSDS
Download (74.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentRhinitis, Allergic, Perennial1

Pharmacoeconomics

Manufacturers
  • Roche palo alto llc
  • Acton pharmaceuticals inc
  • Apotex inc richmond hill
  • Bausch and lomb pharmaceuticals inc
  • Qpharma llc
  • Ivax research inc
  • Teva branded pharmaceutical products r and d inc
Packagers
  • 3M Health Care
  • Apotex Inc.
  • Bausch & Lomb Inc.
  • Dispensing Solutions
  • Elan Pharmaceuticals Inc.
  • Forest Pharmaceuticals
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmedix
  • Physicians Total Care Inc.
  • QPharm Inc.
  • Rising Pharmaceuticals
  • Teva Pharmaceutical Industries Ltd.
Dosage forms
FormRouteStrength
Aerosol, meteredRespiratory (inhalation)250 ug/1
Aerosol, meteredRespiratory (inhalation)80 ug/1
Aerosol, meteredRespiratory (inhalation)250 mcg
SolutionNasal0.25 mg/1mL
Spray, meteredNasal0.25 mg/1mL
Spray, meteredNasal29 ug/1
SolutionNasal29 ug/1
SprayNasal0.025 %
SprayNasal25 mcg
SprayNasal.025 %
Solution; sprayNasal25 mcg
Prices
Unit descriptionCostUnit
Aerobid 250 mcg/act Aerosol 7 gm Inhaler101.95USD inhaler
Aerobid-M 250 mcg/act Aerosol 7 gm Inhaler101.95USD inhaler
Flunisolide 29 mcg/act Solution 25ml Bottle57.16USD bottle
Flunisolide 0.025% Solution 25ml Bottle48.35USD bottle
Aerobid aerosol with adapter14.0USD g
Aerobid-m aerosol with adapter14.0USD g
Flunisolide 29 mcg-0.025% spray2.2USD ml
Nasarel 29 mcg-0.025% spray1.98USD ml
Apo-Flunisolide 0.025 % Spray0.62USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5776433No1998-07-072015-07-07Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)226-230American Cyanamid Co.; British Patent 933,867; August 14, 1963.
water solubilityPractically insolubleNot Available
logP1.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0374 mg/mLALOGPS
logP2.2ALOGPS
logP1.56ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)13.73ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area93.06 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity111.89 m3·mol-1ChemAxon
Polarizability44.88 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9865
Blood Brain Barrier+0.9683
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.7912
P-glycoprotein inhibitor INon-inhibitor0.5674
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.8304
CYP450 2C9 substrateNon-substrate0.8679
CYP450 2D6 substrateNon-substrate0.8856
CYP450 3A4 substrateSubstrate0.6964
CYP450 1A2 substrateNon-inhibitor0.9327
CYP450 2C9 inhibitorNon-inhibitor0.9394
CYP450 2D6 inhibitorNon-inhibitor0.9559
CYP450 2C19 inhibitorNon-inhibitor0.9311
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8806
Ames testNon AMES toxic0.7682
CarcinogenicityNon-carcinogens0.9174
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.7033 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9838
hERG inhibition (predictor II)Non-inhibitor0.671
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00di-3980000000-62e8761f1d0a95a28586

Taxonomy

Description
This compound belongs to the class of organic compounds known as 21-hydroxysteroids. These are steroids carrying a hydroxyl group at the 21-position of the steroid backbone.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Hydroxysteroids
Direct Parent
21-hydroxysteroids
Alternative Parents
Gluco/mineralocorticoids, progestogins and derivatives / 20-oxosteroids / 11-beta-hydroxysteroids / 3-oxo delta-1,4-steroids / Halogenated steroids / Delta-1,4-steroids / Ketals / 1,3-dioxolanes / Alpha-hydroxy ketones / Secondary alcohols
show 8 more
Substituents
Progestogin-skeleton / 21-hydroxysteroid / Pregnane-skeleton / 20-oxosteroid / 3-oxo-delta-1,4-steroid / 3-oxosteroid / 6-halo-steroid / Halo-steroid / 11-hydroxysteroid / 11-beta-hydroxysteroid
show 24 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
11beta-hydroxy steroid, cyclic ketal, 20-oxo steroid, fluorinated steroid, 3-oxo-Delta(1),Delta(4)-steroid, 21-hydroxy steroid (CHEBI:5106)

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. Hochhaus G, Moellmann HW: Binding affinities of rimexolone (ORG 6216), flunisolide and their putative metabolites for the glucocorticoid receptor of human synovial tissue. Agents Actions. 1990 Jun;30(3-4):377-80. [PubMed:2386110]
  2. Johnson M: Development of fluticasone propionate and comparison with other inhaled corticosteroids. J Allergy Clin Immunol. 1998 Apr;101(4 Pt 2):S434-9. [PubMed:9563368]
  3. Valotis A, Hogger P: Significant receptor affinities of metabolites and a degradation product of mometasone furoate. Respir Res. 2004 Jul 22;5:7. [PubMed:15285788]
  4. Hogger P, Erpenstein U, Rohdewald P, Sorg C: Biochemical characterization of a glucocorticoid-induced membrane protein (RM3/1) in human monocytes and its application as model system for ranking glucocorticoid potency. Pharm Res. 1998 Feb;15(2):296-302. [PubMed:9523318]
  5. Badia L, Lund V: Topical corticosteroids in nasal polyposis. Drugs. 2001;61(5):573-8. [PubMed:11368283]
  6. Philibert D, Bouchoux F, Cerede E, Corallo F, Allaire JM: [Pharmacologic study of the glucocorticoid activity of flunisolide compared with other steroids in the rat]. Allerg Immunol (Paris). 1993 Feb;25(2):77-81. [PubMed:8466638]
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inducer
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. Litt J. (2016). Litt's Drug eruption & reaction manual (22nd ed.). CRC Press LLc.

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 04:39