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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

Description

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 TargetPharmacologyConditionPotency

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
CORZIDE

Cmax

ValueDoseCo-administeredAnalytePopulation
27.2 μg/L
5 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens
44.6 μg/L
10 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens
15.4 μg/L
2.5 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
147 μg × h/L
5 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens
250 μg × h/L
10 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens
75 μg × h/L
2.5 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
8.4 h
5 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens
8.4 h
10 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens
8.6 h
2.5 mg single, oral
BENDROFLUMETHIAZIDE plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
6%
BENDROFLUMETHIAZIDE plasma
Homo sapiens

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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.