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

Molecular Formula	C17H20N2O5S
Molecular Weight	364.416
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 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 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
Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.	2000 Feb 11	10660625
Differential roles of the sodium-calcium exchanger in renin secretion and renal vascular resistance.	2001 Aug	11512025
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
Optical method for quantifying rates of mucus secretion from single submucosal glands.	2001 Aug	11435221
Bumetanide annihilation of amphotericin B-induced apoptosis and cytotoxicity is due to its effect on cellular K+ flux.	2001 Dec	11733461
Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl(-)-dependent mechanism.	2001 Dec	11698253
Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium.	2001 Jan	11133877
Vasopressin regulates water flow in a rat cortical collecting duct cell line not containing known aquaporins.	2001 Jan 1	11155210
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
Application of multiple response optimization technique to extended release formulations design.	2001 Jun 15	11516509
Corneal endothelial NKCC: molecular identification, location, and contribution to fluid transport.	2001 Mar	11171568
Gramicidin-perforated patch analysis on HCO3- secretion through a forskolin-activated anion channel in rat parotid intralobular duct cells.	2001 Mar 1	11284200
Vacuolation induced by VacA toxin of Helicobacter pylori requires the intracellular accumulation of membrane permeant bases, Cl(-) and water.	2001 Nov 23	11728476
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
Prostanoids stimulate K secretion and Cl secretion in guinea pig distal colon via distinct pathways.	2001 Oct	11557519
Spontaneous water secretion in T84 cells: effects of STa enterotoxin, bumetanide, VIP, forskolin, and A-23187.	2001 Sep	11518694
Thermogenesis induced by intravenous infusion of hypertonic solutions in the rat.	2001 Sep 1	11533148
Manipulation of chloride flux affects histamine-induced contraction in rabbit basilar artery.	2002 Apr	11893580
Na(+)/K(+)/Cl(-) cotransporter activates mitogen-activated protein kinase in fibroblasts and lymphocytes.	2002 Feb	11807827
Activation of NKCC1 by hyperosmotic stress in human tracheal epithelial cells involves PKC-delta and ERK.	2002 Feb 13	11909643
Effects of butyrate on active sodium and chloride transport in rat and rabbit distal colon.	2002 Feb 15	11850510

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:23:24 UTC 2023` Edited by `admin` on `Fri Dec 15 15:23:24 UTC 2023`
Record UNII	0Y2S3XUQ5H
Record Status	`Validated (UNII)`
Record Version

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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