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Identification
NameFurosemide
Accession NumberDB00695  (APRD00608, DB07799)
Typesmall molecule
Groupsapproved
Description

A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
FrusemideNot AvailableFormer BAN
FurosemidNot AvailableNot Available
FurosemidaSpanishINN
FurosemiduPolishNot Available
FurosemidumLatinINN
SaltsNot Available
Brand names
NameCompany
FrumexNot Available
FrusenexNot Available
LasixSanofi
Brand mixturesNot Available
Categories
CAS number54-31-9
WeightAverage: 330.744
Monoisotopic: 330.007719869
Chemical FormulaC12H11ClN2O5S
InChI KeyInChIKey=ZZUFCTLCJUWOSV-UHFFFAOYSA-N
InChI
InChI=1S/C12H11ClN2O5S/c13-9-5-10(15-6-7-2-1-3-20-7)8(12(16)17)4-11(9)21(14,18)19/h1-5,15H,6H2,(H,16,17)(H2,14,18,19)
IUPAC Name
4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoic acid
SMILES
NS(=O)(=O)C1=C(Cl)C=C(NCC2=CC=CO2)C(=C1)C(O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentAminobenzenesulfonamides
Alternative parentsAminobenzoic Acid Derivatives; Benzoic Acids; Benzoyl Derivatives; Chlorobenzenes; Aryl Chlorides; Sulfonyls; Furans; Sulfonamides; Polyamines; Carboxylic Acids; Enolates; Secondary Amines; Organochlorides
Substituentsbenzoic acid; benzoic acid or derivative; benzoyl; chlorobenzene; aryl halide; aryl chloride; sulfonic acid derivative; sulfonamide; furan; sulfonyl; enolate; polyamine; secondary amine; carboxylic acid; carboxylic acid derivative; amine; organohalogen; organonitrogen compound; organochloride
Classification descriptionThis compound belongs to the aminobenzenesulfonamides. These are organic compounds containing a benzenesulfonamide moiety with an amine group attached to the benzene ring.
Pharmacology
IndicationFor the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and renal disease, including the nephrotic syndrome. Also for the treatment of hypertension alone or in combination with other antihypertensive agents.
PharmacodynamicsFurosemide, a sulfonamide-type loop diuretic structurally related to bumetanide, is used to manage hypertension and edema associated with congestive heart failure, cirrhosis, and renal disease, including the nephrotic syndrome.
Mechanism of actionFurosemide, a loop diuretic, inhibits water reabsorption in the nephron by blocking the sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of the loop of Henle. This is achieved through competitive inhibition at the chloride binding site on the cotransporter, thus preventing the transport of sodium from the lumen of the loop of Henle into the basolateral interstitium. Consequently, the lumen becomes more hypertonic while the interstitium becomes less hypertonic, which in turn diminishes the osmotic gradient for water reabsorption throughout the nephron. Because the thick ascending limb is responsible for 25% of sodium reabsorption in the nephron, furosemide is a very potent diuretic.
Absorption60% absorbed in patients with normal renal function
Volume of distributionNot Available
Protein binding95% bound to plasma proteins
Metabolism

Only a small amount is hepatically metabolized to the defurfurylated derivative, 4-chloro-5-sulfamoylanthranilic acid.

SubstrateEnzymesProduct
Furosemide
    4-chloro-5-sulfamoylanthranilic acidDetails
    Route of eliminationFurosemide is excreted in urine. Significantly more furosemide is excreted in urine following the I.V. injection than after the tablet or oral solution.
    Half life2 hours
    ClearanceNot Available
    ToxicityProfound diuresis may cause fluid and electrolyte depletion. Excessive dehydration and potassium depletion may occur. Excessive diuresis may cause rapid weight loss, orthostatic hypotension or acute hypotensive episodes. May also cause tinnitus, reversible or permanent hearing loss or reversible deafness.
    Affected organisms
    • Humans and other mammals
    Pathways
    PathwayCategorySMPDB ID
    Furosemide Action PathwayDrug actionSMP00115
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 0.9155
    Blood Brain Barrier - 0.8833
    Caco-2 permeable - 0.6436
    P-glycoprotein substrate Non-substrate 0.8775
    P-glycoprotein inhibitor I Non-inhibitor 0.9272
    P-glycoprotein inhibitor II Non-inhibitor 0.8382
    Renal organic cation transporter Non-inhibitor 0.924
    CYP450 2C9 substrate Non-substrate 0.6878
    CYP450 2D6 substrate Non-substrate 0.8351
    CYP450 3A4 substrate Non-substrate 0.6789
    CYP450 1A2 substrate Non-inhibitor 0.9045
    CYP450 2C9 substrate Non-inhibitor 0.907
    CYP450 2D6 substrate Non-inhibitor 0.9231
    CYP450 2C19 substrate Non-inhibitor 0.9025
    CYP450 3A4 substrate Non-inhibitor 0.9602
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6885
    Ames test Non AMES toxic 0.9132
    Carcinogenicity Non-carcinogens 0.6469
    Biodegradation Not ready biodegradable 0.9881
    Rat acute toxicity 2.1362 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.9342
    hERG inhibition (predictor II) Non-inhibitor 0.8525
    Pharmacoeconomics
    Manufacturers
    • Abraxis pharmaceutical products
    • App pharmaceuticals llc
    • Astrazeneca lp
    • Baxter healthcare corp anesthesia and critical care
    • Hospira inc
    • International medication system
    • Luitpold pharmaceuticals inc
    • Marsam pharmaceuticals llc
    • Organon usa inc
    • Smith and nephew solopak div smith and nephew
    • Warner chilcott div warner lambert co
    • Watson laboratories inc
    • Wockhardt ltd
    • Wyeth ayerst laboratories
    • Sanofi aventis us llc
    • Roxane laboratories inc
    • Wockhardt eu operations (swiss) ag
    • Dava pharmaceuticals inc
    • Excellium pharmaceutical inc
    • International medication systems ltd
    • Ipca laboratories ltd
    • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
    • Kalapharm inc
    • Mutual pharmaceutical co inc
    • Mylan pharmaceuticals inc
    • Sandoz inc
    • Superpharm corp
    • Vintage pharmaceuticals inc
    • County line pharmaceuticals llc
    Packagers
    Dosage forms
    FormRouteStrength
    LiquidIntramuscular
    SolutionIntravenous
    SolutionOral
    TabletOral
    Prices
    Unit descriptionCostUnit
    Hydro 40 40% Foam 150 gm Can182.52USDcan
    Hydro 40 40% Foam 70 gm Can148.99USDcan
    Furosemide 10 mg/ml Solution 60ml Bottle17.99USDbottle
    Furosemide 10 mg/ml Solution 120ml Bottle15.98USDbottle
    Furosemide powder3.51USDg
    Lasix Special 500 mg Tablet3.25USDtablet
    Urex 1 gm tablet2.47USDtablet
    Furosemide 10 mg/ml cartrg1.45USDml
    Lasix 80 mg tablet1.0USDtablet
    Furosemide 10 mg/ml Solution0.9USDml
    Furosemide 10 mg/ml0.75USDml
    Lasix 40 mg tablet0.53USDtablet
    Furosemide 80 mg tablet0.45USDtablet
    Lasix 20 mg tablet0.42USDtablet
    Lasix 10 mg/ml Solution0.3USDml
    CVS Pharmacy diuretic 50 mg softgel0.17USDsoftgel capsule
    Furosemide 40 mg tablet0.16USDtablet
    Furosemide 20 mg tablet0.14USDtablet
    Apo-Furosemide 80 mg Tablet0.13USDtablet
    Novo-Semide 80 mg Tablet0.13USDtablet
    Nat herbal diuretic tablet sa0.1USDtablet
    Apo-Furosemide 40 mg Tablet0.07USDtablet
    Natural herbal diuretic tablet0.07USDtablet
    Novo-Semide 40 mg Tablet0.07USDtablet
    Apo-Furosemide 20 mg Tablet0.05USDtablet
    Novo-Semide 20 mg Tablet0.05USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point295 °CPhysProp
    water solubility73.1 mg/L (at 30 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
    logP2.03SANGSTER (1993)
    logS-3.66ADME Research, USCD
    Caco2 permeability-6.5ADME Research, USCD
    Predicted Properties
    PropertyValueSource
    water solubility1.18e-01 g/lALOGPS
    logP2.71ALOGPS
    logP1.75ChemAxon
    logS-3.5ALOGPS
    pKa (strongest acidic)4.25ChemAxon
    pKa (strongest basic)-1.5ChemAxon
    physiological charge-1ChemAxon
    hydrogen acceptor count5ChemAxon
    hydrogen donor count3ChemAxon
    polar surface area122.63ChemAxon
    rotatable bond count5ChemAxon
    refractivity77.47ChemAxon
    polarizability30.55ChemAxon
    number of rings2ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    Spectra
    References
    Synthesis Reference

    Angelo Signor, Alfredo Guerrato, Giovanni Signor, “Process for the preparation of furosemide.” U.S. Patent US5739361, issued June, 1971.

    US5739361
    General Reference
    1. Rais-Bahrami K, Majd M, Veszelovszky E, Short BL: Use of furosemide and hearing loss in neonatal intensive care survivors. Am J Perinatol. 2004 Aug;21(6):329-32. Pubmed
    2. Korpi ER, Kuner T, Seeburg PH, Luddens H: Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor. Mol Pharmacol. 1995 Feb;47(2):283-9. Pubmed
    3. Tia S, Wang JF, Kotchabhakdi N, Vicini S: Developmental changes of inhibitory synaptic currents in cerebellar granule neurons: role of GABA receptor alpha 6 subunit. J Neurosci. 1996 Jun 1;16(11):3630-40. Pubmed
    4. Wafford KA, Thompson SA, Thomas D, Sikela J, Wilcox AS, Whiting PJ: Functional characterization of human gamma-aminobutyric acidA receptors containing the alpha 4 subunit. Mol Pharmacol. 1996 Sep;50(3):670-8. Pubmed
    External Links
    ResourceLink
    KEGG DrugD00331
    PubChem Compound3440
    PubChem Substance46506779
    ChemSpider3322
    BindingDB25902
    ChEBI47426
    ChEMBLCHEMBL35
    Therapeutic Targets DatabaseDAP000043
    PharmGKBPA449719
    HETFUN
    Drug Product Database2247372
    RxListhttp://www.rxlist.com/cgi/generic/furos.htm
    Drugs.comhttp://www.drugs.com/furosemide.html
    WikipediaFurosemide
    ATC CodesNot Available
    AHFS Codes
    • 40:28.08
    PDB EntriesNot Available
    FDA labelshow(462 KB)
    MSDSshow(74.3 KB)
    Interactions
    Drug Interactions
    Drug
    AmikacinIncreased ototoxicity
    CisplatinIncreased ototoxicity
    ColesevelamBile acid sequestrants such as colesevelam may decrease the absorption of loop diuretics such as furosemide. Monitor for decreased serum concentrations/therapeutic effects of loop diuretics if coadministered with bile acid sequestrants. Separating the administration of doses by 2 or more hours may reduce (but not eliminate) the risk of interaction. The manufacturer of colesevelam recommends that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
    DeslanosidePossible electrolyte variations and arrhythmias
    DigitoxinPossible electrolyte variations and arrhythmias
    DigoxinPossible electrolyte variations and arrhythmias
    EthotoinThe hydantoin decreases the effect of furosemide
    FosphenytoinThe hydantoin decreases the effect of furosemide
    GentamicinIncreased ototoxicity
    GinsengGinseng decreases the therapeutic effect
    IbuprofenThe NSAID, ibuprofen, may antagonize the diuretic and antihypertensive effects of the loop diuretic, furosemide.
    IndacaterolConcomitant therapy may increase the risk of hypokalemia via intracellular shunting. Monitor for adverse effects and especially for cardiovascular effects associated with hypokalemia.
    IndomethacinThe NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, furosemide.
    KanamycinIncreased ototoxicity
    MephenytoinThe hydantoin decreases the effect of furosemide
    NetilmicinIncreased ototoxicity
    PhenytoinThe hydantoin decreases the effect of furosemide
    StreptomycinIncreased ototoxicity
    SulindacThe NSAID, sulindac, may decrease the diuretic and antihypertensive effects of the loop diuretic, furosemide.
    TobramycinIncreased ototoxicity
    TrandolaprilThe loop diuretic, Furosemide, may increase the hypotensive effect of Trandolapril. Furosemide may also increase the nephrotoxicity of Trandolapril.
    TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
    Food Interactions
    • Avoid alcohol.
    • Avoid excess salt/sodium unless otherwise instructed by your physician.
    • Increase potassium intake; add a banana or orange juice; unless instructed otherwise.
    • Take with food to reduce irritation.

    1. Solute carrier family 12 member 1

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Solute carrier family 12 member 1 Q13621 Details

    References:

    1. Brater DC: Pharmacology of diuretics. Am J Med Sci. 2000 Jan;319(1):38-50. Pubmed
    2. Davies DL, Wilson GM: Diuretics: mechanism of action and clinical application. Drugs. 1975;9(3):178-226. Pubmed
    3. Vormfelde SV, Sehrt D, Toliat MR, Schirmer M, Meineke I, Tzvetkov M, Nurnberg P, Brockmoller J: Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9. Epub 2007 Apr 25. Pubmed
    4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

    2. Carbonic anhydrase 2

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Components

    Name UniProt ID Details
    Carbonic anhydrase 2 P00918 Details

    References:

    1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

    1. 6-phosphogluconate dehydrogenase, decarboxylating

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    6-phosphogluconate dehydrogenase, decarboxylating P52209 Details

    References:

    1. Akkemik E, Budak H, Ciftci M: Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study. J Enzyme Inhib Med Chem. 2010 Mar 17. Pubmed
    2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

    1. Serum albumin

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Components

    Name UniProt ID Details
    Serum albumin P02768 Details

    References:

    1. Lebedev AA, Samokrutova OV: [Study of the binding of diuretics by serum proteins according to changes in tryptophan fluorescence] Farmakol Toksikol. 1989 May-Jun;52(3):40-3. Pubmed

    1. Solute carrier family 22 member 6

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor inducer

    Components

    Name UniProt ID Details
    Solute carrier family 22 member 6 Q4U2R8 Details

    References:

    1. Kim GH, Na KY, Kim SY, Joo KW, Oh YK, Chae SW, Endou H, Han JS: Up-regulation of organic anion transporter 1 protein is induced by chronic furosemide or hydrochlorothiazide infusion in rat kidney. Nephrol Dial Transplant. 2003 Aug;18(8):1505-11. Pubmed
    2. Hosoyamada M, Sekine T, Kanai Y, Endou H: Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney. Am J Physiol. 1999 Jan;276(1 Pt 2):F122-8. Pubmed
    3. Lu R, Chan BS, Schuster VL: Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2 Pt 2):F295-303. Pubmed
    4. Uwai Y, Saito H, Hashimoto Y, Inui KI: Interaction and transport of thiazide diuretics, loop diuretics, and acetazolamide via rat renal organic anion transporter rOAT1. J Pharmacol Exp Ther. 2000 Oct;295(1):261-5. Pubmed

    2. Solute carrier family 22 member 5

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Solute carrier family 22 member 5 O76082 Details

    References:

    1. Ohashi R, Tamai I, Yabuuchi H, Nezu JI, Oku A, Sai Y, Shimane M, Tsuji A: Na(+)-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther. 1999 Nov;291(2):778-84. Pubmed

    3. Solute carrier family 22 member 8

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Solute carrier family 22 member 8 Q8TCC7 Details

    References:

    1. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. Pubmed
    2. Kusuhara H, Sekine T, Utsunomiya-Tate N, Tsuda M, Kojima R, Cha SH, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of a new multispecific organic anion transporter from rat brain. J Biol Chem. 1999 May 7;274(19):13675-80. Pubmed

    4. Canalicular multispecific organic anion transporter 1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Canalicular multispecific organic anion transporter 1 Q92887 Details

    References:

    1. Bakos E, Evers R, Sinko E, Varadi A, Borst P, Sarkadi B: Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions. Mol Pharmacol. 2000 Apr;57(4):760-8. Pubmed

    5. Solute carrier organic anion transporter family member 2A1

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Solute carrier organic anion transporter family member 2A1 Q92959 Details

    References:

    1. Kanai N, Lu R, Satriano JA, Bao Y, Wolkoff AW, Schuster VL: Identification and characterization of a prostaglandin transporter. Science. 1995 May 12;268(5212):866-9. Pubmed

    6. Solute carrier family 22 member 11

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Solute carrier family 22 member 11 Q9NSA0 Details

    References:

    1. Cha SH, Sekine T, Kusuhara H, Yu E, Kim JY, Kim DK, Sugiyama Y, Kanai Y, Endou H: Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. J Biol Chem. 2000 Feb 11;275(6):4507-12. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:11