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 |
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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 Date1983 |
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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Ongoing clinical trials of the pleiotropic effects of statins. | 2005 |
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[Prevention of cardiovascular events by the antihypertensive treatment using amlodipine and perindopril in comparison with the use of atenolol and bendroflumethiazide. The ASCOT (Anglo-Scandinavian Outcomes Trail: blood pressure lowering arm) study results--multicentre, randomised, controlled trial. Landmark in the development of opinions on combination therapy in hypertension? (comment)]. | 2005 Dec |
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A review of Perindopril in the reduction of cardiovascular events. | 2006 |
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Efficacy and safety of 24 weeks of therapy with bendroflumethiazide 1.25 mg/day or 2.5 mg/day and potassium chloride compared with enalapril 10 mg/day and amlodipine 5 mg/day in patients with mild to moderate primary hypertension : a multicentre, randomised, open study. | 2006 |
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Amlodipine plus perindopril was better than atenolol plus bendroflumethiazide for reducing complications in hypertension. | 2006 Apr |
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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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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 |
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Comparison of the effect of diuretics on carotid blood flow in stroke patients. | 2006 Mar |
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Indirect laser-induced fluorescence detection of diuretics separated by capillary electrophoresis. | 2006 Mar |
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Amlodipine plus perindopril was better than atenolol plus bendroflumethiazide for reducing complications in hypertension. | 2006 Mar-Apr |
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Blunted non-nitric oxide vasodilatory neurotransmission in penile arteries from renal hypertensive rats. | 2006 May |
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Aliskiren--an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension. | 2007 |
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Can combining different risk interventions into a single formulation contribute to improved cardiovascular disease risk reduction? The single pill of amlodipine/atorvastatin. | 2007 |
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Calcium channel blockers, angiotensin receptor blockers, and angiotensin-converting enzyme inhibitors: effectiveness in combination with diuretics or beta-blockers for treating hypertension. | 2007 |
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Common pathways of hypercholesterolemia and hypertension leading to atherothrombosis: the need for a global approach in the management of cardiovascular risk factors. | 2007 |
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Multivariate risk assessment and risk score cards in hypertension. | 2007 |
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Manidipine-delapril combination in the management of hypertension. | 2007 |
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Fast quantitative determination of diuretic drugs in tablets and human urine by microchip electrophoresis with native fluorescence detection. | 2007 Aug |
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Maximising antihypertensive effects of angiotensin II receptor blockers with thiazide diuretic combination therapy: focus on irbesartan/hydrochlorothiazide. | 2007 Dec |
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Low-dose quadruple antihypertensive combination: more efficacious than individual agents--a preliminary report. | 2007 Feb |
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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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Obstructive sleep apnoea: a cause of chronic cough. | 2007 Jul 2 |
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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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A second corneal arcus? | 2007 Mar |
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Flecainide cardiotoxicity precipitated by electrolyte imbalance. Caution with thiazide diuretics. | 2007 May |
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Delayed cardiotoxicity in chronic lithium poisoning: discrepancy between serum lithium concentrations and clinical status. | 2007 May |
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[Treating essential hypertension. Are beta blockers still first choice?]. | 2007 May 3 |
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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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Hirshfeld surface analysis of two bendroflumethiazide solvates. | 2007 Nov |
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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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Pseudoneuropathic CPPD arthropathy: magnesium matters. | 2008 Apr |
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Overlapping in vitro and in vivo specificities of the organic anion transporters OAT1 and OAT3 for loop and thiazide diuretics. | 2008 Apr |
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Upregulation of apical sodium-chloride cotransporter and basolateral chloride channels is responsible for the maintenance of salt-sensitive hypertension. | 2008 Aug |
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STOPP (Screening Tool of Older Person's Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment). Consensus validation. | 2008 Feb |
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Economic evaluation of ASCOT-BPLA: antihypertensive treatment with an amlodipine-based regimen is cost effective compared with an atenolol-based regimen. | 2008 Feb |
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[Serious debate on unconventional treatment, thank you]. | 2008 Feb 25 |
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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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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 |
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[Non-serious criticism of unconventional treatment]. | 2008 Jan 28 |
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Acute angiotensin II infusions elicit pressure natriuresis in mice and reduce distal fractional sodium reabsorption. | 2008 Jul |
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Burden and rates of treatment and control of cardiovascular disease risk factors in obesity: the Framingham Heart Study. | 2008 Jul |
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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 |
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Effective management of hypertension with dihydropyridine calcium channel blocker-based combination therapy in patients at high cardiovascular risk. | 2008 May |
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Acetazolamide prevents vacuolar myopathy in skeletal muscle of K(+) -depleted rats. | 2008 May |
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Preparation of novel beta-cyclodextrin chiral stationary phase based on click chemistry. | 2008 May 16 |
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LC-high-resolution multiple stage spectrometric analysis of diuretic compounds Unusual mass fragmentation pathways. | 2008 Sep 29 |
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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ACTIVE MOIETY