Delving into the Latest Updates on Bendroflumethiazide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

6-trifluoromethyl-3-benzyl-7-sulfamyl-3,4-dihydro-1,2,4-benzothiadiazine 1,1-dioxide, Bendrofluazide, Bendroflumethiazide (JAN/USP/INN)

+ [7]

Target

NCC

Mechanism

NCC inhibitors(Thiazide-sensitive sodium-chloride cotransporter inhibitors)

Therapeutic Areas

Nervous System DiseasesCardiovascular DiseasesEndocrinology and Metabolic Disease+ [2]

Active Indication

Diabetes InsipidusEdemaHypertension+ [1]

Inactive Indication-

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Tianjin Century Pharmaceutical Co., Ltd.

Inactive Organization

Apothecon LLC

Drug Highest PhaseApproved

First Approval Date

US (07 Dec 1959),

EdemaHypertension

Regulation-

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Structure

Molecular FormulaC15H14F3N3O4S2

InChIKeyHDWIHXWEUNVBIY-UHFFFAOYSA-N

CAS Registry73-48-3

The principle objective of the study is to determine whether low-renin (i.e. salt sensitive) hypertension at a young age is caused by the kidneys hanging onto too much salt as a result of an over active salt pump in the kidney.
The kidneys have four different salt pumps, and each is blocked by a different type of diuretic (salt losing tablet)If one out of the four is overactive, we would expect patients to respond much better to one diuretic than to the alternatives - rather than responding equally well to all available types of diuretic.

Start Date01 Aug 2006

Sponsor / Collaborator

University of Cambridge

[+1]

NCT00518479 / CompletedNot Applicable

Pathophysiological Mechanisms of Hypertensive LVH:Optimising Regression

Uncontrolled high blood pressure can cause heart muscle 'thickening', and this increases the likelihood of complications and death. The high blood pressure explains some but not all of this increase in heart size. This study will investigate the other causes, and will measure the heart muscle 'thickness' very accurately using the latest and most accurate technique called cardiac magnetic resonance imaging (MRI). The best way to treat this heart thickening remains to be determined. We hope to be able to show that by specifically targeting the cause of heart muscle thickening we can reduce its occurrence more effectively than by other standard means of blood pressure treatment

Start Date01 Sep 2003

Sponsor / Collaborator

University of Leeds

[+1]

100 Clinical Results associated with Bendroflumethiazide

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100 Translational Medicine associated with Bendroflumethiazide

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100 Patents (Medical) associated with Bendroflumethiazide

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726

Literatures (Medical) associated with Bendroflumethiazide

02 Sep 2024·Drug and Chemical Toxicology

Identification, trace level quantification, and in silico assessment of potential genotoxic impurity in Famotidine

Article

Author: Mishra, Vipin Kumar ; Sayyed, Faiz Hussain ; Nalawade, Vighnesh ; Roy, Bappaditya ; Rathod, Nitin

Potential genotoxic impurities in medications are an increasing concern in the pharmaceutical industry and regulatory bodies because of the risk of human carcinogenesis. To prevent the emergence of these impurities, it is crucial to carefully examine not only the final product but also the intermediates and key starting material (KSM) used in drug synthesis. During the related substances analysis of KSM of Famotidine, an unknown impurity in the range of 0.5-1.0% was found prompting the need for isolation and characterization due to the possibility of its to infiltrate into the final product. In this study, the impurity was isolated and characterized as 5-(2-chloroethyl)-3,3-dimethyl-3,4-dihydro-2H-1,2,4,6-thiatriazine 1,1-dioxide using multiple instrumental analysis, uncovering a structural alert that raises concern. Considering the potential impact of impurity on human health, an in silico genotoxicity assessment was established using Derek and Sarah tool in accordance with ICH M7 guideline. Furthermore, molecular docking and molecular dynamics simulation were performed to evaluate the specific interaction of the impurity with DNA. The findings reveal consistent interaction of the impurity with the dG-rich region of the DNA duplex and binding at the minor groove. Both in silico prediction and molecular dynamic study confirmed the genotoxic character of the impurity. The newly discovered impurity in famotidine has not been reported previously, and there is currently no analytical method available for its identification and control. A highly sensitive HPLC-UV method was developed and validated in accordance with ICH requirements, enabling quantification of the impurity at trace level in famotidine ensuring its safe release.

01 Jun 2024·Clinical Pharmacology & Therapeutics

Genetic Determinants of Thiazide‐Induced Hyperuricemia, Hyperglycemia, and Urinary Electrolyte Disturbances – A Genome‐Wide Evaluation of the UK Biobank

Article

Author: Pirmohamed, Munir ; Asiimwe, Innocent G. ; Sofat, Reecha ; Jorgensen, Andrea L. ; the Multimorbidity Mechanism and Therapeutic Research Collaborative ; Walker, Lauren

Thiazide diuretics, widely used in hypertension, cause a variety of adverse reactions, including hyperglycemia, hyperuricemia, and electrolyte abnormalities. In this study, we aimed to identify genetic variants that interact with thiazide‐use to increase the risk of these adverse reactions. Using UK Biobank data, we first performed genomewide variance quantitative trait locus (vQTL) analysis of ~ 6.2 million SNPs on 95,493 unrelated hypertensive White British participants (24,313 on self‐reported bendroflumethiazide treatment at recruitment) for 2 blood (glucose and urate) and 2 urine (potassium and sodium) biomarkers. Second, we conducted direct gene–environment interaction (GEI) tests on the significant (P < 2.5 × 10−9) vQTLs, included a second UK Biobank cohort comprising 13,647 unrelated hypertensive White British participants (3,478 on thiazides other than bendroflumethiazide) and set significance at P = 0.05 divided by the number of vQTL SNPs tested for GEIs. The vQTL analysis identified eight statistically significant SNPs for blood glucose (5 SNPs) and serum urate (3 SNPs), with none being identified for the urinary biomarkers. Two of the SNPs (1 glucose SNP: CDKAL1 intron rs35612982, GEI P = 6.24 × 10−3; and 1 serum urate SNP: SLC2A9 intron rs938564, GEI P = 4.51 × 10−4) demonstrated significant GEI effects in the first, but not the second, cohort. Both genes are biologically plausible candidates, with the SLC2A9‐mediated interaction having been previously reported. In conclusion, we used a two‐stage approach to detect two biologically plausible genetic loci that can interact with thiazides to increase the risk of thiazide‐associated biochemical abnormalities. Understanding how environmental exposures (including medications such as thiazides) and genetics interact, is an important step toward precision medicine and improved patient outcomes.

01 Jan 2024·Annals of Internal Medicine

A Population-Based Cohort Study

Article

Author: Feenstra, Bjarke ; Hviid, Anders ; Melbye, Mads ; Lund, Marie ; Andersson, Niklas Worm ; Wohlfahrt, Jan

BACKGROUNDAccording to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear.OBJECTIVETo estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice.DESIGNPopulation and register-based cohort study using target trial emulation.SETTINGDenmark, 1 January 2014 to 31 October 2018.PARTICIPANTSTwo target trials were emulated among persons aged 40 years or older who had no recent prescription for any antihypertensive drug, had no previous hyponatremia, and were eligible for the studied antihypertensive treatments. The first target trial emulation compared new use of bendroflumethiazide (BFZ) versus a calcium-channel blocker (CCB). The second target trial emulation compared new use of hydrochlorothiazide plus a renin-angiotensin system inhibitor (HCTZ-RASi; that is, combination pill) versus a RASi alone.MEASUREMENTSTwo-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment-weighted survival curves.RESULTSThe study compared 37 786 new users of BFZ with 44 963 of a CCB and 11 943 new users of HCTZ-RASi with 85 784 of a RASi. The 2-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ-RASi. The risk differences were 1.35% (95% CI, 1.04% to 1.66%) between BFZ and CCB and 1.38% (CI, 1.01% to 1.75%) between HCTZ-RASi and RASi; risk differences were higher with older age and higher comorbidity burden. The respective hazard ratios were 3.56 (CI, 2.76 to 4.60) and 4.25 (CI, 3.23 to 5.59) during the first 30 days since treatment initiation and 1.26 (CI, 1.09 to 1.46) and 1.29 (CI, 1.05 to 1.58) after 1 year.LIMITATIONThe study assumed that filled prescriptions equaled drug use, and residual confounding is likely.CONCLUSIONTreatment initiation with thiazide diuretics suggests a more substantial excess risk for hyponatremia, particularly during the first months of treatment, than indicated by drug labeling.PRIMARY FUNDING SOURCEIndependent Research Fund Denmark.

100 Deals associated with Bendroflumethiazide

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External Link

KEGG	Wiki	ATC	Drug Bank
D00650	Bendroflumethiazide	C03AA01	DB00436

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Diabetes Insipidus	CN	Tianjin Century Pharmaceutical Co., Ltd.	01 Jan 1994
Edema	CN	Tianjin Century Pharmaceutical Co., Ltd.	01 Jan 1994
Hypertension	CN	Tianjin Century Pharmaceutical Co., Ltd.	01 Jan 1994
Nephrolithiasis	CN	Tianjin Century Pharmaceutical Co., Ltd.	01 Jan 1994