U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C15H14F3N3O4S2
Molecular Weight 421.415
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BENDROFLUMETHIAZIDE

SMILES

NS(=O)(=O)C1=CC2=C(NC(CC3=CC=CC=C3)NS2(=O)=O)C=C1C(F)(F)F

InChI

InChIKey=HDWIHXWEUNVBIY-UHFFFAOYSA-N
InChI=1S/C15H14F3N3O4S2/c16-15(17,18)10-7-11-13(8-12(10)26(19,22)23)27(24,25)21-14(20-11)6-9-4-2-1-3-5-9/h1-5,7-8,14,20-21H,6H2,(H2,19,22,23)

HIDE SMILES / InChI

Molecular Formula C15H14F3N3O4S2
Molecular Weight 421.415
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Bendroflumethiazide (INN), formerly bendrofluazide (BAN) is a thiazide diuretic used to treat hypertension. CORZIDE (Nadolol and Bendroflumethiazide Tablets) for oral administration combines two antihypertensive agents: CORGARD (nadolol), a nonselective beta-adrenergic blocking agent, and NATURETIN (bendroflumethiazide), a thiazide diuretic-antihypertensive. Bendroflumethiazide works by inhibiting sodium reabsorption at the beginning of the distal convoluted tubule (DCT). Bendroflumethiazide inhibits active chloride reabsorption at the early distal tubule via the Na-Cl cotransporter, resulting in an increase in the excretion of sodium, chloride, and water. Thiazides like bendroflumethiazide also inhibit sodium ion transport across the renal tubular epithelium through binding to the thiazide sensitive sodium-chloride transporter. This results in an increase in potassium excretion via the sodium-potassium exchange mechanism. The antihypertensive mechanism of bendroflumethiazide is less well understood although it may be mediated through its action on carbonic anhydrases in the smooth muscle or through its action on the large-conductance calcium-activated potassium (KCa) channel, also found in the smooth muscle. Thiazides do not affect normal blood pressure. Onset of action of thiazides occurs in two hours and the peak effect at about four hours. Duration of action persists for approximately six to 12 hours. Thiazides are eliminated rapidly by the kidney.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CORZIDE

Approved Use

is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the classes to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with CORZIDE.

Launch Date

4.22668796E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
27.2 μg/L
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
44.6 μg/L
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
15.4 μg/L
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
147 μg × h/L
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
250 μg × h/L
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
75 μg × h/L
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
8.4 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8.4 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8.6 h
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
6%
BENDROFLUMETHIAZIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim
PubMed

PubMed

TitleDatePubMed
Effects of ACE inhibition supplementary to beta blockers and diuretics in early diabetic nephropathy.
1992 Apr
The effect of spray drying solutions of bendroflumethiazide/polyethylene glycol on the physicochemical properties of the resultant materials.
2003 Aug 27
Do pharmaceuticals affect freshwater invertebrates? A study with the cnidarian Hydra vulgaris.
2003 May
The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis.
2003 Sep 8
Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats.
2004 Apr
Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography.
2004 Jan 2
Comparison of the effects of a 7-day period of non-compliance on blood pressure control using three different antihypertensive agents.
2004 Jul
Effects of furosemide and bendroflumethiazide on saliva flow rate and composition.
2004 Jul
Paradoxical antidiuretic effect of thiazides in diabetes insipidus: another piece in the puzzle.
2004 Nov
FI-chemiluminometric study of thiazides by on-line photochemical reaction.
2004 Nov 19
Ongoing clinical trials of the pleiotropic effects of statins.
2005
Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation.
2005 Aug
Interaction of human serum albumin with bendroflumethiazide studied by fluorescence spectroscopy.
2005 Aug 1
Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone?
2005 Dec
[Antihypertensive therapy: campaign of the giants].
2005 Dec 15
Doxazosin versus bendrofluazide: a comparison of the metabolic effects in British South Asians with hypertension.
2005 Jun
[Cardiac arrest following treatment with non-cardiologic QT-interval-increasing medications].
2005 May 2
Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors.
2005 Oct
Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria.
2005 Sep
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial.
2005 Sep 10-16
ASCOT - blood pressure arm confirms efficacy of amlodipine/perindopril (Norvasc)/Coversyl) regimen.
2005 Sep-Oct
A review of Perindopril in the reduction of cardiovascular events.
2006
High-speed gas chromatography in doping control: fast-GC and fast-GC/MS determination of beta-adrenoceptor ligands and diuretics.
2006 Dec
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
Fracture risk and the use of a diuretic (indapamide SR) +/- perindopril: a substudy of the Hypertension in the Very Elderly Trial (HYVET).
2006 Dec 19
Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels.
2006 Jan
Synthesis and application of mono-2A-azido-2A-deoxyperphenylcarbamoylated beta-cyclodextrin and mono-2A-azido-2A-deoxyperacetylated beta-cyclodextrin as chiral stationary phases for high-performance liquid chromatography.
2006 Jan 6
Aliskiren--an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension.
2007
Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: effectiveness in combination with diuretics or beta-blockers for treating hypertension.
2007
Common pathways of hypercholesterolemia and hypertension leading to atherothrombosis: the need for a global approach in the management of cardiovascular risk factors.
2007
Manidipine-delapril combination in the management of hypertension.
2007
Fast quantitative determination of diuretic drugs in tablets and human urine by microchip electrophoresis with native fluorescence detection.
2007 Aug
The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio.
2007 Jul 17
Obstructive sleep apnoea: a cause of chronic cough.
2007 Jul 2
Effects of "newer" and "older" antihypertensive drugs on hemorrheological, platelet, and endothelial factors. A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.
2007 Jun
A second corneal arcus?
2007 Mar
Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics.
2007 May
Delayed cardiotoxicity in chronic lithium poisoning: discrepancy between serum lithium concentrations and clinical status.
2007 May
[Treating essential hypertension. Are beta blockers still first choice?].
2007 May 3
Does the aldosterone:renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study.
2007 May 9
Are patients reliable when self-reporting medication use? Validation of structured drug interviews and home visits by drug analysis and prescription data in acutely hospitalized patients.
2007 Nov
Combined effect of solvent content, temperature and pH on the chromatographic behaviour of ionisable compounds.
2007 Sep 7
Upregulation of apical sodium-chloride cotransporter and basolateral chloride channels is responsible for the maintenance of salt-sensitive hypertension.
2008 Aug
STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation.
2008 Feb
Letter regarding article by Hood et al, "The Spironolactone, Amiloride, Losartan, and Thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio".
2008 Feb 5
[Non-serious criticism of unconventional treatment].
2008 Jan 28
Acute angiotensin II infusions elicit pressure natriuresis in mice and reduce distal fractional sodium reabsorption.
2008 Jul
Burden and rates of treatment and control of cardiovascular disease risk factors in obesity: the Framingham Heart Study.
2008 Jul
Comparison of effects of combined ACE inhibitor and low-dose thiazide diuretic with ACE inhibitor alone on insulin action in patients with hypertension and Type 2 diabetes: a double-blind crossover study.
2008 May
LC-high-resolution multiple stage spectrometric analysis of diuretic compounds Unusual mass fragmentation pathways.
2008 Sep 29
Patents

Patents

Sample Use Guides

The initial dose of CORZIDE (Nadolol and Bendroflumethiazide Tablets) may therefore be the 40 mg/5 mg tablet once daily. When the antihypertensive response is not satisfactory, the dose may be increased by administering the 80 mg/5 mg tablet once daily. When necessary, another antihypertensive agent may be added gradually beginning with 50 percent of the usual recommended starting dose to avoid an excessive fall in blood pressure.
Route of Administration: Oral
In Vitro Use Guide
Incubation in vitro of human recombinant and erythrocyte (RBC) thiopurine methyl transferase (TPMT) with furosemide, bendroflumethiazide and trichlormethiazide demonstrated inhibition of both enzyme preparations, with IC50 values of 170 microM, 360 microM and 1 mM, respectively.
Substance Class Chemical
Created
by admin
on Sun Dec 18 20:57:03 UTC 2022
Edited
by admin
on Sun Dec 18 20:57:03 UTC 2022
Record UNII
5Q52X6ICJI
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BENDROFLUMETHIAZIDE
EP   HSDB   INN   JAN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
INN  
Official Name English
BENDROFLUMETHIAZIDE [MI]
Common Name English
BENDROFLUAZIDE
Common Name English
BENDROFLUMETHIAZIDE [HSDB]
Common Name English
Bendroflumethiazide [WHO-DD]
Common Name English
BENDROFLUMETHIAZIDE [EP IMPURITY]
Common Name English
BENDROFLUMETHIAZIDE [VANDF]
Common Name English
bendroflumethiazide [INN]
Common Name English
BENDROFLUMETHIAZIDE [USP-RS]
Common Name English
NSC-758229
Code English
BENDROFLUMETHIAZIDE [ORANGE BOOK]
Common Name English
NATURETIN
Brand Name English
BENDROFLUMETHIAZIDE [EP MONOGRAPH]
Common Name English
BENDROFLUMETHIAZIDE COMPONENT OF CORZIDE
Common Name English
BENDROFLUMETHIAZIDE [USP MONOGRAPH]
Common Name English
BENDROFLUMETHIAZIDE [MART.]
Common Name English
2H-1,2,4-BENZOTHIADIAZINE-7-SULFONAMIDE, 3,4-DIHYDRO-3-(PHENYLMETHYL)-6-(TRIFLUOROMETHYL)-, 1,1-DIOXIDE, (±)-
Systematic Name English
(±)-3-BENZYL-3,4-DIHYDRO-6-(TRIFLUOROMETHYL)-2H-1,2,4-BENZOTHIADIAZINE-7-SULFONAMIDE 1,1-DIOXIDE
Systematic Name English
BENDROFLUMETHIAZIDE [JAN]
Common Name English
CORZIDE COMPONENT BENDROFLUMETHIAZIDE
Common Name English
Classification Tree Code System Code
NDF-RT N0000175359
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
NCI_THESAURUS C49185
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
WHO-VATC QC03EA13
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
NDF-RT N0000166469
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
WHO-ATC C03EA13
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
NDF-RT N0000175419
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
NDF-RT N0000166469
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
LIVERTOX 95
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
WHO-VATC QC03AA01
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
WHO-ATC C03AA01
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
WHO-VATC QC03AB01
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
WHO-ATC C03AB01
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
Code System Code Type Description
IUPHAR
7122
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
CAS
73-48-3
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
HSDB
3293
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
FDA UNII
5Q52X6ICJI
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
INN
994
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
NCI_THESAURUS
C47410
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
ECHA (EC/EINECS)
200-800-1
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
EVMPD
SUB20550
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
ChEMBL
CHEMBL1684
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
CHEBI
59243
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
DRUG BANK
DB00436
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
MERCK INDEX
M2309
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY Merck Index
RS_ITEM_NUM
1049000
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
PUBCHEM
2315
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
MESH
D001539
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
WIKIPEDIA
BENDROFLUMETHIAZIDE
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
EVMPD
SUB05711MIG
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
RXCUI
1369
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY RxNorm
CHEBI
3013
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
DRUG CENTRAL
305
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
LACTMED
Bendroflumethiazide
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
EPA CompTox
DTXSID5022647
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
NSC
758229
Created by admin on Sun Dec 18 20:57:05 UTC 2022 , Edited by admin on Sun Dec 18 20:57:05 UTC 2022
PRIMARY
DAILYMED
5Q52X6ICJI
Created by admin on Sun Dec 18 20:57:04 UTC 2022 , Edited by admin on Sun Dec 18 20:57:04 UTC 2022
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
ENANTIOMER -> RACEMATE
ENANTIOMER -> RACEMATE
BINDER->LIGAND
BINDING
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC