BUMETANIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H20N2O5S
Molecular Weight	364.416
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCCCNC1=CC(=CC(=C1OC2=CC=CC=C2)S(N)(=O)=O)C(O)=O

InChI

InChIKey=MAEIEVLCKWDQJH-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018225s024lbl.pdf
Curator's Comment: description was created based on several sources, including: http://www.rxlist.com/bumex-drug/side-effects-interactions.htm https://www.drugs.com/cdi/bumetanide.html http://www.wikidoc.org/index.php/Bumetanide_(oral)

Bumetanide is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. It blocks the reabsorption of sodium and fluid from the kidney's tubules. The most frequent clinical adverse reactions considered probably or possibly related to bumetanide are muscle cramps (seen in 1.1% of treated patients), dizziness (1.1%), hypotension (0.8%), headache (0.6%), nausea (0.6%) and encephalopathy (in patients with preexisting liver disease) (0.6%). One or more of these adverse reactions have been reported in approximately 4.1% of patients treated with Bumex (bumetanide). Lithium should generally not be given with diuretics (such as Bumex (bumetanide)) because they reduce its renal clearance and add a high risk of lithium toxicity. Bumex (bumetanide) may potentiate the effect of various antihypertensive drugs, necessitating a reduction in the dosage of these drugs.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Solute carrier family 12 member 2 3 Target ID: P55011 Gene ID: 6558.0 Gene Symbol: SLC12A2 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/16022677 \| https://www.ncbi.nlm.nih.gov/pubmed/11882915/	Inhibitor 8228	3.0 µM [IC50]
Solute carrier family 12 member 4 2 Target ID: Q9UP95\|\|\|O60632 Gene ID: 6560.0 Gene Symbol: SLC12A4 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/16807348	Blocker 534	60.0 µM [IC50]
Solute carrier family 12 member 5 2 Target ID: Q9H2X9 Gene ID: 57468.0 Gene Symbol: SLC12A5 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/16807348	Blocker 534	55.0 µM [IC50]
Solute carrier family 12 member 1 2 Target ID: Q13621 Gene ID: 6557.0 Gene Symbol: SLC12A1 Target Organism: Homo sapiens (Human) Sources: http://www.drugbank.ca/drugs/DB00887 \| https://www.ncbi.nlm.nih.gov/pubmed/26101812	Blocker 534	4.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Edema 22 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018225s024lbl.pdf	Primary		Approved 8360	BUMEX Approved Use Bumetanide Injection is indicated for the treatment of edema associated with congestive heart failure, hepatic and renal disease, including the nephrotic syndrome. Almost equal diuretic response occurs after oral and parenteral administration of bumetanide. Therefore, if impaired gastrointestinal absorption is suspected or oral administration is not practical, bumetanide should be given by the intramuscular or intravenous route. Successful treatment with bumetanide following instances of allergic reactions to furosemide suggests a lack of cross-sensitivity. Launch Date 4.1523839E11

C_max

Value	Dose	Co-administered	Analyte	Population
42 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8312869	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: FASTED
111.38 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
167.34 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/8312869	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: FASTED
258 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.88 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
5% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/22475517	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:		BUMETANIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
3% DRUG LABEL https://nctr-crs.fda.gov/fdalabel/services/spl/set-ids/9bd7a71e-0e78-dae7-e053-2995a90ad110/spl-doc?hl=bumetanide			BUMETANIDE serum	Homo sapiens population: HEALTHY age: NEWBORN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	Disc. AE: Hypokalemia, Anorexia... AEs leading to discontinuation/dose reduction: Hypokalemia (moderate, 14.3%) Anorexia (moderate) Fatigue (moderate) Polyuria (moderate, 4.8%) Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/7040493 Page: p.597	unhealthy, 22-72 n = 18 Health Status: unhealthy Condition: Renal edema Age Group: 22-72 Sex: M+F Population Size: 18 Sources: https://pubmed.ncbi.nlm.nih.gov/7040493 Page: p.597	Sources: https://pubmed.ncbi.nlm.nih.gov/7040493 Page: p.597

AEs

AE	Significance	Dose	Population
Hypokalemia	moderate, 14.3% Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
Polyuria	moderate, 4.8% Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
Anorexia	moderate Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4
Fatigue	moderate Disc. AE	2 mg 2 times / day multiple, oral Recommended Dose: 2 mg, 2 times / day Route: oral Route: multiple Dose: 2 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4	unhealthy, 14–18 n = 21 Health Status: unhealthy Condition: Autism spectrum disorders Age Group: 14–18 Sex: M+F Population Size: 21 Sources: https://pubmed.ncbi.nlm.nih.gov/28291262 Page: p.4

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT1 595 OAT3 636 OAT4 145 OAT2 144	MRP4 75 OAT3 333 OATP2 11 P-gp 1527 OAT4 76 OAT2 111

Drug as perpetrator

Target	Modality	Activity
OAT4 145	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	modest [IC50 348 uM]
OAT3 638	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 0.75 uM]
OAT1 599	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 7.6 uM]
OAT2 146	inhibitor 3240 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 77.5 uM]

Drug as victim

Target	Modality	Activity
P-gp 1527	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/28192112/	no
MRP4 75	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT2 111	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/15901346/	yes
OAT3 333	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT4 76	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes
OATP2 11	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3213	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3213
ChemicalBook	CB9382992	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9382992
MolPort	MolPort-003-666-390	https://www.molport.com/shop/molecule-link/MolPort-003-666-390
Selleck Chemicals	Bumetanide	http://www.selleckchem.com/products/Bumetanide.html
ZINC	ZINC000003813061	http://zinc15.docking.org/substances/ZINC000003813061
eMolecules	535080	https://www.emolecules.com/cgi-bin/more?vid=535080

PubMed

Title	Date	PubMed
Diuretic therapy and resistance in congestive heart failure.	2001	11805380
Differential roles of the sodium-calcium exchanger in renin secretion and renal vascular resistance.	2001 Aug	11512025
Effects of thiazide- and loop-diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study.	2001 Aug	11489064
Loop diuretics and in vitro relaxation of human fetal and newborn mouse airways.	2001 Aug	11477215
"Avian-type" renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates.	2001 Aug	11473651
Protection of ischemic myocardium in diabetics by inhibition of electroneutral Na+-K+-2Cl- cotransporter.	2001 Aug	11454552
Insulin-independent, MAPK-dependent stimulation of NKCC activity in skeletal muscle.	2001 Aug	11448861
Cl(-)-dependent secretory mechanisms in isolated rat bile duct epithelial units.	2001 Aug	11447024
Functional and molecular characterization of the K-Cl cotransporter of Xenopus laevis oocytes.	2001 Aug	11443066
Alterations in airway ion transport in NKCC1-deficient mice.	2001 Aug	11443061
Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle.	2001 Aug	11443057
Regional differences in ciliary epithelial cell transport properties.	2001 Aug 1	11547344
Contribution of the Na-K-Cl cotransporter on GABA(A) receptor-mediated presynaptic depolarization in excitatory nerve terminals.	2001 Aug 15	11487619
Cisplatin-induced apoptosis of mesothelioma cells is affected by potassium ion flux modulator amphotericin B and bumetanide.	2001 Aug 15	11477563
Potentiation of urinary atrial natriuretic peptide interferes with macula densa function.	2001 Aug 15	11476744
Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism.	2001 Dec	11698253
Liquid and ion transport by fetal airway and lung epithelia of mice deficient in sodium-potassium-2-chloride transporter.	2001 Jul	11472970
Effects of the potassium channel blocker barium on sodium and potassium transport in the rat loop of Henle in vivo.	2001 Jul	11445825
Forskolin activation of apical Cl- channel and Na+/K+/2Cl- cotransporter via a PTK-dependent pathway in renal epithelium.	2001 Jul 27	11467832
Na+-K+-Cl- cotransporter in rat focal cerebral ischemia.	2001 Jun	11488540
Two further British families with the 'cryohydrocytosis' form of hereditary stomatocytosis.	2001 Jun	11442486
Application of multiple response optimization technique to extended release formulations design.	2001 Jun 15	11516509
Pharmacokinetics and pharmacodynamics of intravenous bumetanide in mutant Nagase analbuminemic rats: importance of globulin binding for the pharmacodynamic effects.	2001 May	11745917
HCO3- potentiates the cAMP-dependent secretory response of the human distal colon through a DIDS-sensitive pathway.	2001 May	11417223
Localization of a Na(+)-K(+)-2Cl(-) cotransporter in the rabbit lens.	2001 Nov	11747367
Role of Cl- current in endothelin-1-induced contraction in rabbit basilar artery.	2001 Nov	11668078
Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl(-) and water.	2001 Nov 23	11728476
Ion transport and ligand binding by the Na-K-Cl cotransporter, structure-function studies.	2001 Oct	11913460
Ionic mechanisms of GABA-induced long-term potentiation in the rat superior colliculus.	2001 Oct	11685402
Mechanism(s) of chloride transport in human distal colonic apical membrane vesicles.	2001 Oct	11680599
Quantitative determination of the loop diuretic bumetanide in urine and pharmaceuticals by high-performance liquid chromatography with amperometric detection.	2001 Oct	11669367
Indirectly gated Cl(-)-dependent Cl(-) channels sense physiological changes of extracellular chloride in the leech.	2001 Oct	11600643
Ion transport by sheep distal airways in a miniature chamber.	2001 Oct	11557607
Prostanoids stimulate K secretion and Cl secretion in guinea pig distal colon via distinct pathways.	2001 Oct	11557519
Selective inhibition of Cl(-) conductance in toad skin by blockers of Cl(-) channels and transporters.	2001 Oct	11546659
Loop diuretics alter the diurnal rhythm of endogenous parathyroid hormone secretion. A randomized-controlled study on the effects of loop- and thiazide-diuretics on the diurnal rhythms of calcitropic hormones and biochemical bone markers in postmenopausal women.	2001 Sep	11589718
Apoptosis in post-streptococcal glomerulonephritis.	2001 Sep	11532120
Spontaneous water secretion in T84 cells: effects of STa enterotoxin, bumetanide, VIP, forskolin, and A-23187.	2001 Sep	11518694
Mechanism of substance P-induced liquid secretion across bronchial epithelium.	2001 Sep	11504691
Thermogenesis induced by intravenous infusion of hypertonic solutions in the rat.	2001 Sep 1	11533148
Contribution of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) to transepithelial transport of H(+), NH(4)(+), K(+), and Na(+) in rat outer medullary collecting duct.	2002 Apr	11912241
Renal Na-K-Cl cotransporter NKCC2 in Dahl salt-sensitive rats.	2002 Apr	11910309
NKCC2: a drug target in hypertension.	2002 Apr	11910291
Chloride transport in rabbit esophageal epithelial cells.	2002 Apr	11897626
Na(+)/K(+)/Cl(-) cotransporter activates mitogen-activated protein kinase in fibroblasts and lymphocytes.	2002 Feb	11807827
Activation of ion secretion via proteinase-activated receptor-2 in human colon.	2002 Feb	11804840
Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells.	2002 Feb	11792627
Intrinsic optical signals in the rat optic nerve: role for K(+) uptake via NKCC1 and swelling of astrocytes.	2002 Feb	11754210
Rat NKCC2/NKCC1 cotransporter selectivity for loop diuretic drugs.	2002 Mar	11882915
Functional properties of the apical Na+-K+-2Cl- cotransporter isoforms.	2002 Mar 29	11790783

Patents

Sample Use Guides

In Vivo Use Guide

The usual total daily dosage of Bumetanide is 0.5 mg to 2 mg and in most patients is given as a single dose.

Route of Administration: Other

In Vitro Use Guide

10 uM of bumetanide reduced amplitude and frequency of ictal-like events (ILE) induced by 8.5 mM K(+), but it increased the frequency of ILE induced by 1 microM kainate.

Name

Type

Language

BUMETANIDE

Official Name

English

3-(BUTYLAMINO)-4-PHENOXY-5-SULFAMOYLBENZOIC ACID.

Common Name

English

BUMETANIDE [MI]

Common Name

English

BUMETANIDE [EP MONOGRAPH]

Common Name

English

RO 10-6338

Code

English

BUMETANIDE [VANDF]

Common Name

English

RO-10-6338

Code

English

S-95008.

Code

English

BUMETANIDE [USP-RS]

Common Name

English

BUMETANIDE [ORANGE BOOK]

Common Name

English

BENZOIC ACID, 3-(AMINOSULFONYL)-5-(BUTYLAMINO)-4-PHENOXY-

Common Name

English

BUMETANIDE [USAN]

Common Name

English

BUMETANIDE [EP IMPURITY]

Common Name

English

S95008.

Code

English

RO-106338

Code

English

BUMEX

Brand Name

English

Bumetanide [WHO-DD]

Common Name

English

bumetanide [INN]

Common Name

English

BUMETANIDE [MART.]

Common Name

English

BUMETANIDE [USP MONOGRAPH]

Common Name

English

BUMETANIDE [JAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175590