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Identification
NameBumetanide
Accession NumberDB00887  (APRD00294)
Typesmall molecule
Groupsapproved
Description

A sulfamyl diuretic. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
3-(Aminosulfonyl)-5-(butylamino)-4-phenoxybenzoic acidNot AvailableNot Available
3-Butylamino-4-(phenoxy)-5-sulfamoylbenzoic acidNot AvailableNot Available
3-Butylamino-4-phenoxy-5-sulfamoyl-benzoic acidNot AvailableNot Available
3-Butylamino-4-phenoxy-5-sulfamoylbenzoic acidNot AvailableNot Available
BumetanidaSpanishINN
BumetanidumLatinINN
SaltsNot Available
Brand names
NameCompany
BumetanideHospira, Inc.
BumexF. Hoffmann-La Roche Ltd.
BurinexF. Hoffmann-La Roche Ltd.
FordiuranLEO Pharma A/S
LunetoronDaiichi Sankyo
Brand mixturesNot Available
Categories
CAS number28395-03-1
WeightAverage: 364.416
Monoisotopic: 364.10929245
Chemical FormulaC17H20N2O5S
InChI KeyMAEIEVLCKWDQJH-UHFFFAOYSA-N
InChI
InChI=1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23)
IUPAC Name
3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid
SMILES
CCCCNC1=C(OC2=CC=CC=C2)C(=CC(=C1)C(O)=O)S(N)(=O)=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassBenzenesulfonamides
Direct parentAminobenzenesulfonamides
Alternative parentsDiarylethers; Aminobenzoic Acid Derivatives; Benzoic Acids; Benzoyl Derivatives; Phenol Ethers; Sulfonyls; Sulfonamides; Secondary Amines; Carboxylic Acids; Polyamines; Enolates
Substituentsbenzoic acid; benzoic acid or derivative; phenol ether; benzoyl; sulfonyl; sulfonic acid derivative; sulfonamide; enolate; secondary amine; polyamine; carboxylic acid derivative; carboxylic acid; ether; amine; organonitrogen compound
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, hepatic and renal disease including the nephrotic syndrome.
PharmacodynamicsBumetanide is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in patients in whom high doses of furosemide are ineffective. There is however no reason not to use bumetanide as a first choice drug. The main difference between the two substances is in bioavailability. It is said to be a more predictable diuretic, meaning that the predictable absorption is reflected in a more predictable effect. Bumetanide is 40 times more potent than furosemide (for patients with normal renal function).
Mechanism of actionBumetanide interferes with renal cAMP and/or inhibits the sodium-potassium ATPase pump. Bumetanide appears to block the active reabsorption of chloride and possibly sodium in the ascending loop of Henle, altering electrolyte transfer in the proximal tubule. This results in excretion of sodium, chloride, and water and, hence, diuresis.
AbsorptionBumetanide is completely absorbed (80%), and the absorption is not altered when taken with food. Bioavailability is almost complete.
Volume of distributionNot Available
Protein binding97%
Metabolism

45% is secreted unchanged. Urinary and biliary metabolites are formed by oxidation of the N-butyl side chain.

Route of eliminationOral administration of carbon-14 labeled Bumex to human volunteers revealed that 81% of the administered radioactivity was excreted in the urine, 45% of it as unchanged drug. Biliary excretion of Bumex amounted to only 2% of the administered dose.
Half life60-90 minutes
Clearance
  • 0.2 – 1.1 mL/min/kg [preterm and full-term neonates with respiratory disorders]
  • 2.17 mL/min/kg [neonates receiving bumetanide for volume overload]
  • 1.8 +/- 0.3 mL/min/kg [geriatric subjects]
  • 2.9 +/- 0.2 mL/min/kg [younger subjects]
ToxicityOverdosage can lead to acute profound water loss, volume and electrolyte depletion, dehydration, reduction of blood volume and circulatory collapse with a possibility of vascular thrombosis and embolism. Electrolyte depletion may be manifested by weakness, dizziness, mental confusion, anorexia, lethargy, vomiting and cramps. Treatment consists of replacement of fluid and electrolyte losses by careful monitoring of the urine and electrolyte output and serum electrolyte levels.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Bumetanide Action PathwayDrug actionSMP00088
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9967
Blood Brain Barrier - 0.6636
Caco-2 permeable - 0.6492
P-glycoprotein substrate Non-substrate 0.509
P-glycoprotein inhibitor I Non-inhibitor 0.8765
P-glycoprotein inhibitor II Non-inhibitor 0.8103
Renal organic cation transporter Non-inhibitor 0.8966
CYP450 2C9 substrate Non-substrate 0.6368
CYP450 2D6 substrate Non-substrate 0.7656
CYP450 3A4 substrate Non-substrate 0.6059
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7344
Ames test Non AMES toxic 0.6794
Carcinogenicity Non-carcinogens 0.7294
Biodegradation Not ready biodegradable 0.9837
Rat acute toxicity 1.8148 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9319
hERG inhibition (predictor II) Non-inhibitor 0.8591
Pharmacoeconomics
Manufacturers
  • Baxter healthcare corp anesthesia and critical care
  • Bedford laboratories div ben venue laboratories inc
  • Hospira inc
  • Teva parenteral medicines inc
  • Validus pharmaceuticals inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Sandoz inc
Packagers
Dosage forms
FormRouteStrength
TabletOral
Prices
Unit descriptionCostUnit
Bumex 2 mg tablet1.65USDtablet
Bumetanide 2 mg tablet1.04USDtablet
Bumex 1 mg tablet0.98USDtablet
Bumex 0.5 mg tablet0.7USDtablet
Bumetanide 1 mg tablet0.51USDtablet
Bumetanide 0.5 mg tablet0.38USDtablet
Bumetanide 0.25 mg/ml vial0.25USDml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point230-231Felt, P.W.; US. Patent 3,634,583; January 11, 1972; assigned to Lovens Kemiske Fabrik Produktionsaktieselskab, Denmark.
water solubility>20 mg/mL (in base)Not Available
logP2.6Not Available
Predicted Properties
PropertyValueSource
water solubility2.57e-02 g/lALOGPS
logP3.44ALOGPS
logP2.42ChemAxon
logS-4.2ALOGPS
pKa (strongest acidic)4.69ChemAxon
pKa (strongest basic)2.7ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area118.72ChemAxon
rotatable bond count8ChemAxon
refractivity95.78ChemAxon
polarizability37.21ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Felt, P.W.; US. Patent 3,634,583; January 11, 1972; assigned to Lovens Kemiske Fabrik
Produktionsaktieselskab, Denmark.

General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD00247
PubChem Compound2471
PubChem Substance46508147
ChemSpider2377
BindingDB25903
ChEBI3213
ChEMBLCHEMBL1072
Therapeutic Targets DatabaseDAP000361
PharmGKBPA448682
Drug Product Database728284
RxListhttp://www.rxlist.com/cgi/generic2/bumetan.htm
Drugs.comhttp://www.drugs.com/cdi/bumetanide.html
PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/bum1058.shtml
WikipediaBumetanide
ATC CodesC03CA02
AHFS Codes
  • 40:28.08
PDB EntriesNot Available
FDA labelshow(206 KB)
MSDSshow(72.8 KB)
Interactions
Drug Interactions
Drug
AmikacinIncreased ototoxicity
CisplatinIncreased ototoxicity
ColesevelamBile acid sequestrants such as colesevelam may decrease the absorption of loop diuretics such as bumetanide. 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
GentamicinIncreased ototoxicity
GinsengGinseng may decrease the therapeutic effect of diuretic, bumetanide.
IbuprofenThe NSAID, ibuprofen, may antagonize the diuretic and antihypertensive effects of the loop diuretic, bumetanide.
IndomethacinThe NSAID, indomethacin, may decrease the diuretic and antihypertensive effects of the loop diuretic, bumetanide.
KanamycinIncreased ototoxicity
NetilmicinIncreased ototoxicity
StreptomycinIncreased ototoxicity
SulindacThe NSAID, sulindac, decreases the diuretic and antihypertensive effects of the loop diuretic, bumetanide.
TobramycinIncreased ototoxicity
TrandolaprilThe loop diuretic, Bumetanide, may increase the hypotensive effect of Trandolapril. Bumetanide may also increase the nephrotoxicity of Trandolapril.
TreprostinilAdditive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Food Interactions
  • 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. Thakker RV: Chloride channels in renal disease. Adv Nephrol Necker Hosp. 1999;29:289-98. Pubmed
  2. Karolyi L, Koch MC, Grzeschik KH, Seyberth HW: The molecular genetic approach to “Bartter’s syndrome”. J Mol Med. 1998 Apr;76(5):317-25. Pubmed
  3. Thakker RV: The role of renal chloride channel mutations in kidney stone disease and nephrocalcinosis. Curr Opin Nephrol Hypertens. 1998 Jul;7(4):385-8. Pubmed
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  5. Long P, Mercer A, Begum R, Stephens GJ, Sihra TS, Jovanovic JN: Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate Release. J Biol Chem. 2009 Mar 27;284(13):8726-37. Epub 2009 Jan 13. Pubmed

2. Solute carrier family 12 member 2

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 2 P55011 Details

References:

  1. Panet R, Marcus M, Atlan H: Overexpression of the Na()/K()/Cl(-) cotransporter gene induces cell proliferation and phenotypic transformation in mouse fibroblasts. J Cell Physiol. 2000 Jan;182(1):109-18. Pubmed
  2. Evans RL, Park K, Turner RJ, Watson GE, Nguyen HV, Dennett MR, Hand AR, Flagella M, Shull GE, Melvin JE: Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice. J Biol Chem. 2000 Sep 1;275(35):26720-6. Pubmed
  3. Wall SM, Fischer MP, Mehta P, Hassell KA, Park SJ: Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD. Am J Physiol Renal Physiol. 2001 May;280(5):F913-21. Pubmed
  4. Akar F, Jiang G, Paul RJ, O’Neill WC: Contractile regulation of the Na()-K()-2Cl(-) cotransporter in vascular smooth muscle. Am J Physiol Cell Physiol. 2001 Aug;281(2):C579-84. Pubmed
  5. Jiang G, Klein JD, O’Neill WC: Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism. Am J Physiol Cell Physiol. 2001 Dec;281(6):C1948-53. Pubmed

3. Solute carrier family 12 member 4

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 4 Q9UP95 Details

References:

  1. Jean-Xavier C, Pflieger JF, Liabeuf S, Vinay L: Inhibitory postsynaptic potentials in lumbar motoneurons remain depolarizing after neonatal spinal cord transection in the rat. J Neurophysiol. 2006 Nov;96(5):2274-81. Epub 2006 Jun 28. Pubmed
  2. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. Pubmed

4. Solute carrier family 12 member 5

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 12 member 5 Q9H2X9 Details

References:

  1. Reid KH, Guo SZ, Iyer VG: Agents which block potassium-chloride cotransport prevent sound-triggered seizures in post-ischemic audiogenic seizure-prone rats. Brain Res. 2000 May 2;864(1):134-7. Pubmed

5. Cystic fibrosis transmembrane conductance regulator

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Cystic fibrosis transmembrane conductance regulator P13569 Details

References:

  1. Reddy MM, Quinton PM: Bumetanide blocks CFTR GCl in the native sweat duct. Am J Physiol. 1999 Jan;276(1 Pt 1):C231-7. Pubmed

Enzymes

1. Prostaglandin G/H synthase 2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inducer

Components

Name UniProt ID Details
Prostaglandin G/H synthase 2 P35354 Details

References:

  1. Cheng HF, Wang JL, Zhang MZ, McKanna JA, Harris RC: Role of p38 in the regulation of renal cortical cyclooxygenase-2 expression by extracellular chloride. J Clin Invest. 2000 Sep;106(5):681-8. Pubmed

Transporters

1. Sodium/bile acid cotransporter

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Sodium/bile acid cotransporter Q14973 Details

References:

  1. Hagenbuch B, Stieger B, Foguet M, Lubbert H, Meier PJ: Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10629-33. Pubmed
  2. Platte HD, Honscha W, Schuh K, Petzinger E: Functional characterization of the hepatic sodium-dependent taurocholate transporter stably transfected into an immortalized liver-derived cell line and V79 fibroblasts. Eur J Cell Biol. 1996 May;70(1):54-60. Pubmed

2. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

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

References:

  1. Race JE, Grassl SM, Williams WJ, Holtzman EJ: Molecular cloning and characterization of two novel human renal organic anion transporters (hOAT1 and hOAT3). Biochem Biophys Res Commun. 1999 Feb 16;255(2):508-14. Pubmed
  2. 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

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. 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

5. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

References:

  1. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. Pubmed

6. Solute carrier organic anion transporter family member 1A2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
Solute carrier organic anion transporter family member 1A2 P46721 Details

References:

  1. Horz JA, Honscha W, Petzinger E: Bumetanide is not transported by the Ntcp or by the oatp: evidence for a third organic anion transporter in rat liver cells. Biochim Biophys Acta. 1996 Apr 19;1300(2):114-8. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on April 02, 2014 09:42