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
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)
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
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL3038495 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14766795 |
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Target ID: CHEMBL1876 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10894798 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | CORZIDE Approved Useis 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 Date4.22668796E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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27.2 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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 |
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44.6 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
147 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
8.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7056277 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6369882 |
BENDROFLUMETHIAZIDE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
PubMed
Title | Date | PubMed |
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Quinine-mediated disseminated intravascular coagulation. | 1999 Jul |
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A comparison of selected antihypertensives and the use of conventional vs ambulatory blood pressure in the detection and treatment of hypertension. | 2001 |
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Unsuspected nephrogenic diabetes insipidus. | 2001 Jul 14 |
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Nebivolol reverses endothelial dysfunction in essential hypertension: a randomized, double-blind, crossover study. | 2001 Jul 31 |
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Determination and characterization of diuretics in human urine by liquid chromatography coupled to pneumatically assisted electrospray ionization mass spectrometry. | 2001 Jun |
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Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs. | 2002 Apr |
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Results of the pilot study for the Hypertension in the Very Elderly Trial. | 2003 Dec |
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The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis. | 2003 Sep 8 |
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Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography. | 2004 Jan 2 |
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Comparison of the effects of a 7-day period of non-compliance on blood pressure control using three different antihypertensive agents. | 2004 Jul |
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Effects of furosemide and bendroflumethiazide on saliva flow rate and composition. | 2004 Jul |
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A case of hypertension and hyperkalaemia. | 2004 Jun |
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Paradoxical antidiuretic effect of thiazides in diabetes insipidus: another piece in the puzzle. | 2004 Nov |
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FI-chemiluminometric study of thiazides by on-line photochemical reaction. | 2004 Nov 19 |
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Ongoing clinical trials of the pleiotropic effects of statins. | 2005 |
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Physicochemical evaluation of PVP-thiazide diuretic interactions in co-spray-dried composites--analysis of glass transition composition relationships. | 2005 Apr |
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[Antihypertensive therapy: campaign of the giants]. | 2005 Dec 15 |
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Aldosterone-to-renin ratio, arterial stiffness, and the response to aldosterone antagonism in essential hypertension. | 2005 Jan |
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[Old or new antihypertensives--which are better?]. | 2005 Mar 31 |
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Enhanced renoprotective effects of ultrahigh doses of irbesartan in patients with type 2 diabetes and microalbuminuria. | 2005 Sep |
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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 |
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[The most recent study into blood pressure lowering by amlodipine: the beginning of the end for the beta-blockers]. | 2006 Apr 22 |
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High-speed gas chromatography in doping control: fast-GC and fast-GC/MS determination of beta-adrenoceptor ligands and diuretics. | 2006 Dec |
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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 |
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Thiazide diuretic prescription and electrolyte abnormalities in primary care. | 2006 Jan |
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Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. | 2006 Jan |
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Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats. | 2006 May |
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Treatments with losartan or enalapril are equally sensitive to deterioration in renal function from cyclooxygenase inhibition. | 2007 Feb |
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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 |
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Effects of "newer" and "older" antihypertensive drugs on hemorrheological, platelet, and endothelial factors. A substudy of the Anglo-Scandinavian Cardiac Outcomes Trial. | 2007 Jun |
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Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics. | 2007 May |
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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 |
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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 |
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Combined effect of solvent content, temperature and pH on the chromatographic behaviour of ionisable compounds. | 2007 Sep 7 |
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The Sandwell Project: a controlled evaluation of a programme of targeted screening for prevention of cardiovascular disease in primary care. | 2008 Feb 25 |
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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
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8866635
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.
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N0000175359
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C49185
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QC03EA13
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N0000166469
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N0000166469
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95
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C03AB01
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D001539
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BENDROFLUMETHIAZIDE
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Bendroflumethiazide
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ACTIVE MOIETY