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 |
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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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Vasoactive peptides and procollagen propeptides in patients with hypertension in relation to cardiac hypertrophy and diastolic heart failure: design of the study and patient characteristics. | 2001 Aug |
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Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators. | 2001 Jun |
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Monitoring one-year compliance to antihypertension medication in the Seychelles. | 2002 |
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Phototoxicity to diuretics and antidiabetics in the cultured keratinocyte cell line HaCaT: evaluation by clonogenic assay and single cell gel electrophoresis Comet assay). | 2002 Apr |
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Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs. | 2002 Apr |
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Skeletal muscle magnesium content is correlated with plasma glucose concentration in patients with essential hypertension treated with lisinopril or bendrofluazide. | 2002 Aug |
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Use of the photo-micronucleus assay in Chinese hamster V79 cells to study photochemical genotoxicity. | 2002 Aug 26 |
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Von Willebrand factor, soluble P-selectin, and target organ damage in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). | 2002 Jul |
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Paradoxical antidiuretic effect of thiazides in diabetes insipidus: another piece in the puzzle. | 2004 Nov |
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The systemic haemodynamic and cerebral autoregulatory effects of bendrofluazide in the subacute post-stroke period. | 2004 Oct |
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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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Differential cognitive outcomes in the Hypertensive Old People in Edinburgh study. | 2005 Mar 15 |
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[Old or new antihypertensives--which are better?]. | 2005 Mar 31 |
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Cyclooxygenase inhibition causes marked impairment of renal function in elderly subjects treated with diuretics and ACE-inhibitors. | 2005 Oct |
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A review of Perindopril in the reduction of cardiovascular events. | 2006 |
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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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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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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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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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A second corneal arcus? | 2007 Mar |
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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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[Serious debate on unconventional treatment, thank you]. | 2008 Feb 25 |
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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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Acetazolamide prevents vacuolar myopathy in skeletal muscle of K(+) -depleted rats. | 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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