BUMETANIDE SODIUM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H19N2O5S.Na
Molecular Weight	386.398
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[Na+].CCCCNC1=C(OC2=CC=CC=C2)C(=CC(=C1)C([O-])=O)S(N)(=O)=O

InChI

InChIKey=QDFGOJHAQZEYQL-UHFFFAOYSA-M

InChI=1S/C17H20N2O5S.Na/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);/q;+1/p-1

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 8297	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 537	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 537	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 537	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 8429	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 1983

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 599 OAT3 642 OAT4 146 OAT2 145	MRP4 77 OAT3 339 OATP2 11 P-gp 1537 OAT4 78 OAT2 115

Drug as perpetrator

Target	Modality	Activity
OAT4 146	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	modest [IC50 348 uM]
OAT3 644	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 0.75 uM]
OAT1 603	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 7.6 uM]
OAT2 147	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 77.5 uM]

Drug as victim

Target	Modality	Activity
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/28192112/	no
MRP4 77	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT2 115	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/15901346/	yes
OAT3 339	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT4 78	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes
OATP2 11	substrate 3367 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
Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4.	2000 Sep 29	10913127
Alternatively spliced isoform of apical Na(+)-K(+)-Cl(-) cotransporter gene encodes a furosemide-sensitive Na(+)-Cl(-)cotransporter.	2001 Apr	11249848
Differential roles of the sodium-calcium exchanger in renin secretion and renal vascular resistance.	2001 Aug	11512025
Functional and molecular characterization of the K-Cl cotransporter of Xenopus laevis oocytes.	2001 Aug	11443066
Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle.	2001 Aug	11443057
Optical method for quantifying rates of mucus secretion from single submucosal glands.	2001 Aug	11435221
Potentiation of urinary atrial natriuretic peptide interferes with macula densa function.	2001 Aug 15	11476744
An integrative, in situ approach to examining K+ flux in resting skeletal muscle.	2001 Dec	11824943
Effect of short-term treatment with bumetanide, quinapril and low-sodium diet on dogs with moderate congestive heart failure.	2001 Feb	11256277
Activation of Na(+), K(+), Cl(-)-cotransport mediates intracellular Ca(2+) increase and apoptosis induced by Pinacidil in HepG2 human hepatoblastoma cells.	2001 Feb 23	11181077
Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins.	2001 Jan	11123367
The effect of serotonin on airway transepithelial sodium ion pathways.	2001 Jan 26	11165222
Liquid and ion transport by fetal airway and lung epithelia of mice deficient in sodium-potassium-2-chloride transporter.	2001 Jul	11472970
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
Determination and characterization of diuretics in human urine by liquid chromatography coupled to pneumatically assisted electrospray ionization mass spectrometry.	2001 Jun	11433538
cAMP-dependent fluid secretion in rat inner medullary collecting ducts.	2001 Jun	11352842
Application of multiple response optimization technique to extended release formulations design.	2001 Jun 15	11516509
K(+) transport in red blood cells from human umbilical cord.	2001 Jun 6	11406100
Diverging effects of 5-HT3 receptor antagonists ondansetron and granisetron on estramustine-inhibited cellular potassium transport.	2001 May	11393584
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713
Ethanol-induced swelling in neonatal rat primary astrocyte cultures.	2001 May 11	11334801
Ion transport and ligand binding by the Na-K-Cl cotransporter, structure-function studies.	2001 Oct	11913460
Mechanism of substance P-induced liquid secretion across bronchial epithelium.	2001 Sep	11504691
NKCC2: a drug target in hypertension.	2002 Apr	11910291
Chloride transport in rabbit esophageal epithelial cells.	2002 Apr	11897626
Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex.	2002 Feb 14	11856535
Basolateral PAR-2 receptors mediate KCl secretion and inhibition of Na+ absorption in the mouse distal colon.	2002 Feb 15	11850514
Rat NKCC2/NKCC1 cotransporter selectivity for loop diuretic drugs.	2002 Mar	11882915
The flavonol quercetin activates basolateral K(+) channels in rat distal colon epithelium.	2002 Mar	11877325
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 SODIUM

Common Name

English

BUMETANIDE SODIUM SALT

Common Name

English

SODIUM 3-(AMINOSULFONYL)-5-(BUTYLAMINO)-4-PHENOXYBENZOATE

Systematic Name

English

BENZOIC ACID, 3-(AMINOSULFONYL)-5-(BUTYLAMINO)-4-PHENOXY-, SODIUM SALT (1:1)

Systematic Name

English

Code System Code Type Description

EPA CompTox

DTXSID60182634