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
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
Quinine-mediated disseminated intravascular coagulation.
1999 Jul
A comparison of selected antihypertensives and the use of conventional vs ambulatory blood pressure in the detection and treatment of hypertension.
2001
Unsuspected nephrogenic diabetes insipidus.
2001 Jul 14
Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study.
2001 Jul 31
Determination and characterization of diuretics in human urine by liquid chromatography coupled to pneumatically assisted electrospray ionization mass spectrometry.
2001 Jun
Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs.
2002 Apr
Results of the pilot study for the Hypertension in the Very Elderly Trial.
2003 Dec
The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis.
2003 Sep 8
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
A case of hypertension and hyperkalaemia.
2004 Jun
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
Physicochemical evaluation of PVP-thiazide diuretic interactions in co-spray-dried composites--analysis of glass transition composition relationships.
2005 Apr
[Antihypertensive therapy: campaign of the giants].
2005 Dec 15
Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension.
2005 Jan
[Old or new antihypertensives--which are better?].
2005 Mar 31
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
[The most recent study into blood pressure lowering by amlodipine: the beginning of the end for the beta-blockers].
2006 Apr 22
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
Thiazide diuretic prescription and electrolyte abnormalities in primary care.
2006 Jan
Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels.
2006 Jan
Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats.
2006 May
Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition.
2007 Feb
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
Effects of "newer" and "older" antihypertensive drugs on hemorrheological, platelet, and endothelial factors. A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.
2007 Jun
Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics.
2007 May
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
The Sandwell Project: a controlled evaluation of a programme of targeted screening for prevention of cardiovascular disease in primary care.
2008 Feb 25
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
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.
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 Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
NCI_THESAURUS C49185
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
WHO-VATC QC03EA13
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
NDF-RT N0000166469
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
WHO-ATC C03EA13
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
NDF-RT N0000175419
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
NDF-RT N0000166469
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
LIVERTOX 95
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
WHO-VATC QC03AA01
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
WHO-ATC C03AA01
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
WHO-VATC QC03AB01
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
WHO-ATC C03AB01
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
Code System Code Type Description
IUPHAR
7122
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
CAS
73-48-3
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
HSDB
3293
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
FDA UNII
5Q52X6ICJI
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
INN
994
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
NCI_THESAURUS
C47410
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
SMS_ID
100000092763
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
ECHA (EC/EINECS)
200-800-1
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
EVMPD
SUB20550
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
ChEMBL
CHEMBL1684
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
CHEBI
59243
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
DRUG BANK
DB00436
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
MERCK INDEX
M2309
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY Merck Index
RS_ITEM_NUM
1049000
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
PUBCHEM
2315
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
MESH
D001539
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
WIKIPEDIA
BENDROFLUMETHIAZIDE
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
EVMPD
SUB05711MIG
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
RXCUI
1369
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY RxNorm
CHEBI
3013
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
DRUG CENTRAL
305
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
LACTMED
Bendroflumethiazide
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
EPA CompTox
DTXSID5022647
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
NSC
758229
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY
DAILYMED
5Q52X6ICJI
Created by admin on Thu Jul 06 23:11:01 UTC 2023 , Edited by admin on Thu Jul 06 23:11:01 UTC 2023
PRIMARY