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 8146	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 530	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 530	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 530	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 8307	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 584 OAT3 625 OAT4 145 OAT2 144	MRP4 75 OAT3 328 OATP2 6 P-gp 1491 OAT4 76 OAT2 111

Drug as perpetrator

Target	Modality	Activity
OAT4 145	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	modest [IC50 348 uM]
OAT3 627	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 0.75 uM]
OAT1 588	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 7.6 uM]
OAT2 146	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes [IC50 77.5 uM]

Drug as victim

Target	Modality	Activity
P-gp 1491	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/28192112/	no
MRP4 75	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT2 111	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/15901346/	yes
OAT3 328	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/25449033/	yes
OAT4 76	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/14610216/	yes
OATP2 6	substrate 3264 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 a new multispecific organic anion transporter from rat brain.	1999 May 7	10224140
Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta.	2000 Feb 11	10660625
Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4.	2000 Sep 29	10913127
Diuretic therapy and resistance in congestive heart failure.	2001	11805380
Solubilization and stability of bumetanide in vehicles for intranasal administration, a pilot study.	2001	11416987
Effect of chloride channel blockers on anti-IgE-stimulated histamine and IL-4/IL-13 release from human basophils.	2001 Apr	11411600
Insulin increases the turnover rate of Na+-K+-ATPase in human fibroblasts.	2001 Apr	11245608
Effects of thiazide- and loop-diuretics, alone or in combination, on calcitropic hormones and biochemical bone markers: a randomized controlled study.	2001 Aug	11489064
"Avian-type" renal medullary tubule organization causes immaturity of urine-concentrating ability in neonates.	2001 Aug	11473651
Contractile regulation of the Na(+)-K(+)-2Cl(-) cotransporter in vascular smooth muscle.	2001 Aug	11443057
Cisplatin-induced apoptosis of mesothelioma cells is affected by potassium ion flux modulator amphotericin B and bumetanide.	2001 Aug 15	11477563
An integrative, in situ approach to examining K+ flux in resting skeletal muscle.	2001 Dec	11824943
Effects of isoprostanes and prostanoids on porcine small intestine.	2001 Feb	11160628
Reduced Na-K pump but increased Na-K-2Cl cotransporter in aorta of streptozotocin-induced diabetic rat.	2001 Feb	11158986
Adrenergic receptor activated ion transport in human fetal retinal pigment epithelium.	2001 Jan	11133877
Hepatic uptake of synthetic chlorogenic acid derivatives by the organic anion transport proteins.	2001 Jan	11123367
Vasopressin regulates water flow in a rat cortical collecting duct cell line not containing known aquaporins.	2001 Jan 1	11155210
The effect of serotonin on airway transepithelial sodium ion pathways.	2001 Jan 26	11165222
HCO3- transport in relation to mucus secretion from submucosal glands.	2001 Jul	11875272
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
Epinephrine-induced increases in [Ca2+](in) and KCl-coupled fluid absorption in bovine RPE.	2001 Jul	11431462
Endogenous and exogenous Na-K-Cl cotransporter expression in a low K-resistant mutant MDCK cell line.	2001 Jun	11350756
Application of multiple response optimization technique to extended release formulations design.	2001 Jun 15	11516509
Na+ reabsorption in cultured rat epididymal epithelium via the Na+/nucleoside cotransporter.	2001 Mar	11207189
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
HCO3- potentiates the cAMP-dependent secretory response of the human distal colon through a DIDS-sensitive pathway.	2001 May	11417223
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
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
Chloride transport in rabbit esophageal epithelial cells.	2002 Apr	11897626
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
Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells.	2002 Feb	11792627
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
Effects of butyrate on active sodium and chloride transport in rat and rabbit distal colon.	2002 Feb 15	11850510
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 16:57:56 UTC 2022` Edited by `admin` on `Fri Dec 16 16:57:56 UTC 2022`
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