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)
Molecular Formula | C15H14F3N3O4S2 |
Molecular Weight | 421.415 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
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 |
---|---|---|---|---|
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 |
|
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 |
---|---|---|
Effects of ACE inhibition supplementary to beta blockers and diuretics in early diabetic nephropathy. | 1992 Apr |
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The effect of spray drying solutions of bendroflumethiazide/polyethylene glycol on the physicochemical properties of the resultant materials. | 2003 Aug 27 |
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Do pharmaceuticals affect freshwater invertebrates? A study with the cnidarian Hydra vulgaris. | 2003 May |
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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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Carbonic anhydrase inhibitors are specific openers of skeletal muscle BK channel of K+-deficient rats. | 2004 Apr |
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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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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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Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation. | 2005 Aug |
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Interaction of human serum albumin with bendroflumethiazide studied by fluorescence spectroscopy. | 2005 Aug 1 |
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Does aldosterone-to-renin ratio predict the antihypertensive effect of the aldosterone antagonist spironolactone? | 2005 Dec |
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[Antihypertensive therapy: campaign of the giants]. | 2005 Dec 15 |
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Doxazosin versus bendrofluazide: a comparison of the metabolic effects in British South Asians with hypertension. | 2005 Jun |
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[Cardiac arrest following treatment with non-cardiologic QT-interval-increasing medications]. | 2005 May 2 |
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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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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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ASCOT - blood pressure arm confirms efficacy of amlodipine/perindopril (Norvasc)/Coversyl) regimen. | 2005 Sep-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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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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Carbonic anhydrase inhibitors ameliorate the symptoms of hypokalaemic periodic paralysis in rats by opening the muscular Ca2+-activated-K+ channels. | 2006 Jan |
|
Synthesis and application of mono-2A-azido-2A-deoxyperphenylcarbamoylated beta-cyclodextrin and mono-2A-azido-2A-deoxyperacetylated beta-cyclodextrin as chiral stationary phases for high-performance liquid chromatography. | 2006 Jan 6 |
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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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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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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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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 |
|
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 |
|
A second corneal arcus? | 2007 Mar |
|
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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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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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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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 |
|
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sun Dec 18 20:57:03 UTC 2022
by
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on
Sun Dec 18 20:57:03 UTC 2022
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Record UNII |
5Q52X6ICJI
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Record Status |
Validated (UNII)
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Record Version |
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NDF-RT |
N0000175359
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NCI_THESAURUS |
C49185
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WHO-VATC |
QC03EA13
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NDF-RT |
N0000166469
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WHO-ATC |
C03EA13
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NDF-RT |
N0000175419
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N0000166469
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LIVERTOX |
95
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WHO-VATC |
QC03AA01
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C03AA01
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WHO-VATC |
QC03AB01
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WHO-ATC |
C03AB01
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7122
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73-48-3
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3293
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5Q52X6ICJI
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994
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C47410
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200-800-1
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SUB20550
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CHEMBL1684
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59243
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DB00436
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M2309
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1049000
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2315
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D001539
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BENDROFLUMETHIAZIDE
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SUB05711MIG
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1369
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3013
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305
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Bendroflumethiazide
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DTXSID5022647
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758229
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5Q52X6ICJI
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TARGET -> INHIBITOR | |||
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ENANTIOMER -> RACEMATE | |||
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ENANTIOMER -> RACEMATE | |||
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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IMPURITY -> PARENT |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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