HYDROFLUMETHIAZIDE

US Previously Marketed

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H8F3N3O4S2
Molecular Weight	331.292
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NS(=O)(=O)C1=C(C=C2NCNS(=O)(=O)C2=C1)C(F)(F)F

InChI

InChIKey=DMDGGSIALPNSEE-UHFFFAOYSA-N

InChI=1S/C8H8F3N3O4S2/c9-8(10,11)4-1-5-7(2-6(4)19(12,15)16)20(17,18)14-3-13-5/h1-2,13-14H,3H2,(H2,12,15,16)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00774
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/saluron.html

Hydroflumethiazide is a thiazide diuretic that inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, Hydroflumethiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron. Hydroflumethiazide is used as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy. Also used in the management of hypertension either as the sole therapeutic agent or to enhance the effect of other antihypertensive drugs in the more severe forms of hypertension.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium-(potassium)-chloride cotransporter 2 15 Target ID: CHEMBL1874 Sources: http://www.drugbank.ca/drugs/DB00774	Inhibitor 8297
Carbonic anhydrase I 62 Target ID: CHEMBL261 Sources: http://www.drugbank.ca/drugs/DB00774	Inhibitor 8297
Thiazide-sensitive sodium-chloride cotransporter 28 Target ID: CHEMBL1876 Sources: http://www.genome.jp/dbget-bin/www_bget?D00654	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Edema 22 Sources: https://www.drugs.com/pro/saluron.html	Primary		Approved 8429	SALURON Approved Use Saluron® is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis and corticosteroid and estrogen therapy. Saluron® has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. Saluron® is indicated in the management of hypertension, either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. Launch Date 1959
Hypertension 567 Sources: https://www.drugs.com/pro/saluron.html	Primary		Approved 8429	SALURON Approved Use Saluron® is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis and corticosteroid and estrogen therapy. Saluron® has also been found useful in edema due to various forms of renal dysfunction, such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure. Saluron® is indicated in the management of hypertension, either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension. Launch Date 1959

C_max

Value	Dose	Co-administered	Analyte	Population
0.389 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/833338/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		HYDROFLUMETHIAZIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1.717 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/833338/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROFLUMETHIAZIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
13.12 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/729604/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROFLUMETHIAZIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
9.83 μM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/729604/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROFLUMETHIAZIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/833338/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROFLUMETHIAZIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
9.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/729604/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROFLUMETHIAZIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
16.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/729604/	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	HYDROFLUMETHIAZIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
0.8 g single, oral Highest studied dose Dose: 0.8 g Route: oral Route: single Dose: 0.8 g Sources: https://pubmed.ncbi.nlm.nih.gov/13706413 Page: p.56	unhealthy, 32 - 80 n = 16 Health Status: unhealthy Condition: Edema Age Group: 32 - 80 Sex: M+F Population Size: 16 Sources: https://pubmed.ncbi.nlm.nih.gov/13706413 Page: p.56	Sources: https://pubmed.ncbi.nlm.nih.gov/13706413 Page: p.56

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	activator 22

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	OAT1 326

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C9 1819	activator 214 Sources: https://pubmed.ncbi.nlm.nih.gov/17559204/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
OAT1 326	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/32918656/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5784	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5784
ChemicalBook	CB5416596	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5416596
MolPort	MolPort-001-771-232	https://www.molport.com/shop/molecule-link/MolPort-001-771-232
ZINC	ZINC000000897225	http://zinc15.docking.org/substances/ZINC000000897225
eMolecules	539394	https://www.emolecules.com/cgi-bin/more?vid=539394

PubMed

Title	Date	PubMed
Gas-phase behaviour of negative ions produced from thiazidic diuretics under electrospray conditions.	2002 Sep	12271437
Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer.	2003 Apr	12695909
Indexing powder patterns in physical form screening: instrumentation and data quality.	2003 Sep	12950010
FI-chemiluminometric study of thiazides by on-line photochemical reaction.	2004 Nov 19	15533660
Physicochemical evaluation of PVP-thiazide diuretic interactions in co-spray-dried composites--analysis of glass transition composition relationships.	2005 Apr	15784345
High-speed gas chromatography in doping control: fast-GC and fast-GC/MS determination of beta-adrenoceptor ligands and diuretics.	2006 Dec	17305237
Fast gas chromatographic/mass spectrometric determination of diuretics and masking agents in human urine: Development and validation of a productive screening protocol for antidoping analysis.	2006 Dec 1	17027009
Diuretics: from classical carbonic anhydrase inhibitors to novel applications of the sulfonamides.	2008	18336309
Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited--old leads for new applications?	2008 Jul 21	18600270
Chloro-thia-zide-pyridine (1/3).	2008 May 17	21202618
Rapid determination of losartan and losartan acid in human plasma by multiplexed LC-MS/MS.	2009 Oct	19750501
Generic sample preparation combined with high-resolution liquid chromatography-time-of-flight mass spectrometry for unification of urine screening in doping-control laboratories.	2010 Apr	20155493
Interfacing on-line solid phase extraction with monolithic column multisyringe chromatography and chemiluminescence detection: An effective tool for fast, sensitive and selective determination of thiazide diuretics.	2010 Jan 15	20006096

Patents

Sample Use Guides

In Vivo Use Guide

In the treatment of edema, the usual initial dose is 50 to 200 mg daily, in 1 or 2 divided doses, reduced to a dose of 25 to 50 mg on alternate days or intermittently. In the treatment of hypertension, the usual dose is 25 to 50 mg daily in 1 or 2 divided doses, either alone, or in conjunction with other antihypertensive agents. A suggested initial dose for children is 1 mg per kg of body weight daily, reduced for maintenance.

Route of Administration: Oral

In Vitro Use Guide

Hydroflumethiazide at concentrations ranging from 1 to 50 ug/mL stimulated the normal secretion of glucagon, insulin, and somatostatin in a dose-dependent manner in isolated perfused pancreas of normal and alloxan diabetic dogs.

Name

Type

Language

HYDROFLUMETHIAZIDE

Official Name

English

HYDROFLUMETHIAZIDE [VANDF]

Common Name

English

3,4-Dihydro-6-(trifluoromethyl)-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide

Systematic Name

English

HYDROFLUMETHIAZIDE [USP MONOGRAPH]

Common Name

English

HYDROFLUMETHIAZIDE [JAN]

Common Name

English

hydroflumethiazide [INN]

Common Name

English

HYDROFLUMETHIAZIDE [MI]

Common Name

English

HYDROFLUMETHIAZIDE [HSDB]

Common Name

English

SALURON

Brand Name

English

Hydroflumethiazide [WHO-DD]

Common Name

English

DIUCARDIN

Brand Name

English

NSC-44627

Code

English

HYDROFLUMETHIAZIDE [ORANGE BOOK]

Common Name

English

HYDROFLUMETHIAZIDE [USP-RS]

Common Name

English

2H-1,2,4-BENZOTHIADIAZINE-7-SULFONAMIDE, 3,4-DIHYDRO-6-(TRIFLUOROMETHYL)-, 1,1-DIOXIDE

Systematic Name

English

HYDROFLUMETHIAZIDE COMPONENT OF SALUTENSIN

Common Name

English

HYDROFLUMETHIAZIDE [MART.]

Common Name

English

SALUTENSIN COMPONENT HYDROFLUMETHIAZIDE

Common Name

English

Classification Tree Code System Code

LIVERTOX

486