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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
DiurapidMibe Jena
DiurinMylan
DiurmesselBiomep
EutensinSanofi
FrumexNot Available
FrusenexNot Available
FrusolRosemont
Furo-PurenActavis
LasixSanofi
SegurilSanofi
Brand mixturesNot Available
Categories
CAS number54-31-9
WeightAverage: 330.744
Monoisotopic: 330.007719869
Chemical FormulaC12H11ClN2O5S
InChI KeyZZUFCTLCJUWOSV-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
Not Available
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 point206U.S. Patent 3,058,882.
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
SpectraMS/MS1D NMR2D NMR
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.

Targets

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

Enzymes

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

Carriers

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

Transporters

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

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