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 acetateN225H64CIH4533-89-5WEGNFRKBIKYVLC-XTLNBZDDSA-N
Flunisolide hemihydrateQK4DYS664X77326-96-6MIXMJCQRHVAJIO-TZHJZOAOSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AerospanAerosol, metered80 ug/1Respiratory (inhalation)Acton Pharmaceuticals, Inc.2012-03-01Not applicableUs
AerospanAerosol, metered80 ug/1Respiratory (inhalation)Meda Pharmaceuticals Ltd2012-03-01Not applicableUs
Bronalide Inhal 250mcg/aemAerosol, metered250 mcgRespiratory (inhalation)Boehringer Ingelheim (Canada) Ltd Ltee1988-12-311999-02-15Canada
Novo-flunisolideSpray25 mcgNasalNovopharm Limited1998-06-302005-08-10Canada
PMS-flunisolideSpray0.025 %NasalPharmascience Inc1994-12-312009-08-27Canada
Ratio-flunisolideSpray25 mcgNasalRatiopharm Inc Division Of Teva Canada Limited1993-12-312010-08-02Canada
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 SpraySpray, metered0.25 mgNasalApotex Corporation2000-03-10Not applicableCanada
FlunisolideSolution.25 mg/mLNasalPhysicians Total Care, Inc.2003-05-23Not applicableUs
FlunisolideSolution.25 mg/mLNasalRemedy Repack2016-02-172017-03-02Us
FlunisolideSpray, metered.25 mg/mLNasalRising Pharmaceuticals2006-08-03Not applicableUs
FlunisolideSolution.25 mg/mLNasalBauch & Lomb Incorporated2002-02-20Not applicableUs
FlunisolideSolution.25 mg/mLNasalRemedy Repack2017-08-16Not applicableUs
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

Pharmacology

Indication

For the maintenance treatment of asthma as a prophylactic therapy.

Structured Indications
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
DrugInteractionDrug group
AmiodaroneThe metabolism of Flunisolide can be decreased when combined with Amiodarone.Approved, Investigational
AprepitantThe serum concentration of Flunisolide can be increased when it is combined with Aprepitant.Approved, Investigational
AtazanavirThe metabolism of Flunisolide can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Flunisolide can be decreased when combined with Atomoxetine.Approved
BoceprevirThe metabolism of Flunisolide can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Flunisolide can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Flunisolide can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe metabolism of Flunisolide can be increased when combined with Carbamazepine.Approved, Investigational
CeritinibThe serum concentration of Flunisolide can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe metabolism of Flunisolide can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Flunisolide can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Flunisolide can be decreased when combined with Clotrimazole.Approved, Vet Approved
CobicistatThe metabolism of Flunisolide can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Flunisolide can be increased when it is combined with Conivaptan.Approved, Investigational
CrizotinibThe metabolism of Flunisolide can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Flunisolide can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
DabrafenibThe serum concentration of Flunisolide can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe metabolism of Flunisolide can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Flunisolide can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Flunisolide can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Flunisolide can be decreased when combined with Delavirdine.Approved
DihydroergotamineThe metabolism of Flunisolide can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Flunisolide can be decreased when combined with Diltiazem.Approved
DoxycyclineThe metabolism of Flunisolide can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Flunisolide can be decreased when combined with Dronedarone.Approved
EnzalutamideThe serum concentration of Flunisolide can be decreased when it is combined with Enzalutamide.Approved
ErythromycinThe metabolism of Flunisolide can be decreased when combined with Erythromycin.Approved, Vet Approved
FluconazoleThe metabolism of Flunisolide can be decreased when combined with Fluconazole.Approved
FluvoxamineThe metabolism of Flunisolide can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Flunisolide can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Flunisolide can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Flunisolide can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Flunisolide can be increased when it is combined with Fusidic Acid.Approved
IdelalisibThe serum concentration of Flunisolide can be increased when it is combined with Idelalisib.Approved
ImatinibThe metabolism of Flunisolide can be decreased when combined with Imatinib.Approved
IndinavirThe metabolism of Flunisolide can be decreased when combined with Indinavir.Approved
IsavuconazoniumThe metabolism of Flunisolide can be decreased when combined with Isavuconazonium.Approved, Investigational
IsradipineThe metabolism of Flunisolide can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Flunisolide can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Flunisolide can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Flunisolide can be decreased when combined with Ketoconazole.Approved, Investigational
LopinavirThe metabolism of Flunisolide can be decreased when combined with Lopinavir.Approved
LovastatinThe metabolism of Flunisolide can be decreased when combined with Lovastatin.Approved, Investigational
LoxapineThe risk or severity of adverse effects can be increased when Flunisolide is combined with Loxapine.Approved
LuliconazoleThe serum concentration of Flunisolide can be increased when it is combined with Luliconazole.Approved
LumacaftorThe metabolism of Flunisolide can be increased when combined with Lumacaftor.Approved
MifepristoneThe serum concentration of Flunisolide can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Flunisolide can be decreased when it is combined with Mitotane.Approved
NefazodoneThe metabolism of Flunisolide can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Flunisolide can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Flunisolide can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Flunisolide can be increased when combined with Nevirapine.Approved
NilotinibThe metabolism of Flunisolide can be decreased when combined with Nilotinib.Approved, Investigational
OlaparibThe metabolism of Flunisolide can be decreased when combined with Olaparib.Approved
OsimertinibThe serum concentration of Flunisolide can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Flunisolide can be increased when it is combined with Palbociclib.Approved
PentobarbitalThe metabolism of Flunisolide can be increased when combined with Pentobarbital.Approved, Vet Approved
PhenobarbitalThe metabolism of Flunisolide can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Flunisolide can be increased when combined with Phenytoin.Approved, Vet Approved
PosaconazoleThe metabolism of Flunisolide can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PrimidoneThe metabolism of Flunisolide can be increased when combined with Primidone.Approved, Vet Approved
RanolazineThe metabolism of Flunisolide can be decreased when combined with Ranolazine.Approved, Investigational
RifabutinThe metabolism of Flunisolide can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Flunisolide can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Flunisolide can be increased when combined with Rifapentine.Approved
RitonavirThe metabolism of Flunisolide can be decreased when combined with Ritonavir.Approved, Investigational
SaquinavirThe metabolism of Flunisolide can be decreased when combined with Saquinavir.Approved, Investigational
SildenafilThe metabolism of Flunisolide can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Flunisolide can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Flunisolide can be increased when it is combined with Simeprevir.Approved
St. John's WortThe serum concentration of Flunisolide can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Flunisolide can be increased when it is combined with Stiripentol.Approved
SulfisoxazoleThe metabolism of Flunisolide can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TelaprevirThe metabolism of Flunisolide can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Flunisolide can be decreased when combined with Telithromycin.Approved
TiclopidineThe metabolism of Flunisolide can be decreased when combined with Ticlopidine.Approved
TocilizumabThe serum concentration of Flunisolide can be decreased when it is combined with Tocilizumab.Approved
VenlafaxineThe metabolism of Flunisolide can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Flunisolide can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Flunisolide can be decreased when combined with Voriconazole.Approved, Investigational
ZiprasidoneThe metabolism of Flunisolide can be decreased when combined with Ziprasidone.Approved
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
HMDB14326
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
Dosage forms
FormRouteStrength
Aerosol, meteredRespiratory (inhalation)80 ug/1
Spray, meteredNasal0.25 mg
Aerosol, meteredRespiratory (inhalation)250 mcg
SolutionNasal.25 mg/mL
Spray, meteredNasal.25 mg/mL
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)
US5776433No1995-07-072015-07-07Us

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
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

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Yes
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 13, 2017 21:49