Identification
- Name
- Torasemide
- Accession Number
- DB00214 (APRD00295, APRD00217)
- Type
- Small Molecule
- Groups
- Approved
- Description
Torasemide (rINN) or torsemide (USAN) is a pyridine-sulfonylurea type loop diuretic mainly used in the management of edema associated with congestive heart failure. It is also used at low doses for the management of hypertension. It is marketed under the brand name Demadex. [Wikipedia]
- Structure
Structure for Torasemide (DB00214)
- Synonyms
- 1-Isopropyl-3-((4-m-toluidino-3-pyridyl)sulfonyl)urea
- Luprac
- N-(((1-Methylethyl)amino)carbonyl)-4-((3-methylphenyl)amino)-3-pyridinesulfonamide
- Torasemida
- Torasemidum
- Torsemide
- External IDs
- AC-4464 / AC4464 / BM02.015
- Product Images
- Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Demadex Tablet 20 mg/1 Oral MEDA Pharmaceuticals 2015-01-01 2018-11-30 US 
Demadex Tablet 20 mg/1 Oral Physicians Total Care, Inc. 2009-10-21 Not applicable US Demadex Tablet 100 mg/1 Oral Roche Pharmaceuticals 2007-02-06 Not applicable US Demadex Tablet 20 mg/1 Oral Meda Pharmaceuticals Inc. 2009-02-20 2009-08-04 US Demadex Tablet 5 mg/1 Oral Roche Pharmaceuticals 2007-02-06 Not applicable US Demadex Injection, solution 10 mg/1mL Intravenous Roche Pharmaceuticals 2007-02-06 Not applicable US Demadex Tablet 10 mg/1 Oral MEDA Pharmaceuticals 2015-01-01 2019-06-30 US Demadex Tablet 20 mg/1 Oral Roche Pharmaceuticals 2007-02-06 Not applicable US Demadex Tablet 10 mg/1 Oral Meda Pharmaceuticals Inc. 2009-02-20 2009-08-04 US Demadex Tablet 100 mg/1 Oral MEDA Pharmaceuticals 2015-01-01 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Torsemide Tablet 20 mg/1 Oral Aphena Pharma Solutions Tennessee, Inc. 2005-03-03 Not applicable US Torsemide Tablet 100 mg/1 Oral Camber Pharmaceuticals 2011-01-01 Not applicable US Torsemide Tablet 20 mg/1 Oral Amerincan Health Packaging 2011-10-19 Not applicable US Torsemide Tablet 5 mg/1 Oral Qualitest 2011-03-22 2016-03-27 US Torsemide Tablet 100 mg/1 Oral Teva 2010-04-19 2011-03-31 US Torsemide Tablet 100 mg/1 Oral Sun Pharmaceutical Industries Limited 2008-02-26 2017-02-18 US Torsemide Tablet 10 mg/1 Oral Aurobindo Pharma 2007-10-17 Not applicable US Torsemide Tablet 100 mg/1 Oral Teva Pharmaceuticals USA, Inc. 2004-10-20 Not applicable US Torsemide Tablet 5 mg/1 Oral Camber Pharmaceuticals 2011-01-01 Not applicable US Torsemide Tablet 10 mg/1 Oral Rising Health, Llc 2007-10-17 Not applicable US - International/Other Brands
- Demadex / Diuver / Examide / Luprac
- Categories
- Amides
- Antihypertensive Agents
- Cardiovascular Agents
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Diuretics
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- High-Ceiling Diuretics
- Hyperglycemia-Associated Agents
- Hypotensive Agents
- Increased Diuresis at Loop of Henle
- Membrane Transport Modulators
- Natriuretic Agents
- Non Potassium Sparing Diuretics
- Sodium Potassium Chloride Symporter Inhibitors
- Sulfonamides
- Sulfones
- Sulfur Compounds
- UNII
- W31X2H97FB
- CAS number
- 56211-40-6
- Weight
- Average: 348.42
Monoisotopic: 348.125611216 - Chemical Formula
- C16H20N4O3S
- InChI Key
- NGBFQHCMQULJNZ-UHFFFAOYSA-N
- InChI
- InChI=1S/C16H20N4O3S/c1-11(2)18-16(21)20-24(22,23)15-10-17-8-7-14(15)19-13-6-4-5-12(3)9-13/h4-11H,1-3H3,(H,17,19)(H2,18,20,21)
- IUPAC Name
- 1-({4-[(3-methylphenyl)amino]pyridin-3-yl}sulfonyl)-3-(propan-2-yl)urea
- SMILES
- CC(C)NC(=O)NS(=O)(=O)C1=C(NC2=CC=CC(C)=C2)C=CN=C1
Pharmacology
- Indication
For the treatment of edema associated with congestive heart failure, renal disease, or hepatic disease. Also for the treatment of hypertension alone or in combination with other antihypertensive agents.
- Associated Conditions
- Pharmacodynamics
Torasemide (INN) or torsemide (USAN) is a novel loop diuretic belonging to pridine sulphonyl urea. It differs form other thiazide diuretics in that a double ring system is incorporated into its structure. Like thiazides, loop diuretics must be secreted into the tubular fluid by proximal tubule cells. In the thick ascending loop Na+ and Cl- reabsorption is accomplished by a Na+/K+/2Cl- symporter. The thick ascending limb has a high reabsorptive capacity and is responsible for reabsorbing 25% of the filtered load of Na+. The loop diuretics act by blocking this symporter. Because of the large absorptive capacity and the amount of Na+ delivered to the ascending limb, loop diuretics have a profound diuretic action. In addition, more distal nephron segments do not have the reabsorptive capacity to compensate for this increased load. The osmotic gradient for water reabsorption is also reduced resulting in an increase in the amount of water excreted.
- Mechanism of action
Torasemide inhibits the Na+/K+/2Cl--carrier system (via interference of the chloride binding site) in the lumen of the thick ascending portion of the loop of Henle, resulting in a decrease in reabsorption of sodium and chloride. This results in an increase in the rate of delivery of tubular fluid and electrolytes to the distal sites of hydrogen and potassium ion secretion, while plasma volume contraction increases aldosterone production. The increased delivery and high aldosterone levels promote sodium reabsorption at the distal tubules, and By increasing the delivery of sodium to the distal renal tubule, torasemide indirectly increases potassium excretion via the sodium-potassium exchange mechanism. Torasemide's effects in other segments of the nephron have not been demonstrated. Thus torasemide increases the urinary excretion of sodium, chloride, and water, but it does not significantly alter glomerular filtration rate, renal plasma flow, or acid-base balance. Torasemide's effects as a antihypertensive are due to its diuretic actions. By reducing extracellular and plasma fluid volume, blood pressure is reduced temporarily, and cardiac output also decreases.
Target Actions Organism ASolute carrier family 12 member 1 inhibitorHuman - Absorption
Rapidly absorbed following oral administration. Absolute bioavailability is 80%. Food has no effect on absorption.
- Volume of distribution
- 12 to 15 L [normal adults or in patients with mild to moderate renal failure or congestive heart failure]
- Protein binding
> 99%
- Metabolism
Metabolized via the hepatic CYP2C8 to 5 metabolites. The major metabolite, M5, is pharmacologically inactive. There are 2 minor metabolites, M1, possessing one-tenth the activity of torasemide, and M3, equal in activity to torasemide. Overall, torasemide appears to account for 80% of the total diuretic activity, while metabolites M1 and M3 account for 9% and 11%, respectively.
- Route of elimination
Torsemide is cleared from the circulation by both hepatic metabolism (approximately 80% of total clearance) and excretion into the urine (approximately 20% of total clearance in patients with normal renal function).
- Half life
3.5 hours
- Clearance
- Not Available
- Toxicity
Symptoms of overdose include dehydration, hypovolemia, hypotension, hyponatremia, hypokalemia, hypochloremic alkalosis, and hemoconcentration. Oral LD50 in rat is 5 g/kg, and intravenous LD50 in rat is 500 mg/kg.
- Affected organisms
- Humans and other mammals
- Pathways
Pathway Category Torsemide Action Pathway Drug action - Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
Drug Interaction 2,4-thiazolidinedione The therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Torasemide. Abediterol The risk or severity of hyperkalemia can be increased when Abediterol is combined with Torasemide. Abiraterone The serum concentration of Torasemide can be increased when it is combined with Abiraterone. Acarbose The therapeutic efficacy of Acarbose can be decreased when used in combination with Torasemide. Acebutolol Torasemide may increase the hypotensive activities of Acebutolol. Aceclofenac The therapeutic efficacy of Torasemide can be decreased when used in combination with Aceclofenac. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Torasemide. Acetyldigitoxin The risk or severity of adverse effects can be increased when Torasemide is combined with Acetyldigitoxin. Acetyldigoxin The risk or severity of adverse effects can be increased when Torasemide is combined with Acetyldigoxin. Acetylsalicylic acid The therapeutic efficacy of Torasemide can be decreased when used in combination with Acetylsalicylic acid. - Food Interactions
- Not Available
References
- Synthesis Reference
Fritz Topfmeier, Gustav Lettenbauer, "Process for the preparation of a stable modification of torasemide." U.S. Patent USRE0345806, issued June, 1975.
USRE0345806- General References
- Dunn CJ, Fitton A, Brogden RN: Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs. 1995 Jan;49(1):121-42. [PubMed:7705212]
- Authors unspecified: FDA approved new drug bulletin: torsemide (Demadex), trimetrexate glucuronate (neuTrexin). RN. 1994 May;57(5):53-6. [PubMed:8197389]
- External Links
- Human Metabolome Database
- HMDB0014359
- KEGG Drug
- D00382
- PubChem Compound
- 41781
- PubChem Substance
- 46504760
- ChemSpider
- 38123
- BindingDB
- 64107
- ChEBI
- 9637
- ChEMBL
- CHEMBL1148
- Therapeutic Targets Database
- DAP000745
- PharmGKB
- PA451733
- RxList
- RxList Drug Page
- PDRhealth
- PDRhealth Drug Page
- Wikipedia
- Torasemide
- ATC Codes
- C03CA04 — TorasemideG01AE10 — Combinations of sulfonamides
- MSDS
- Download (110 KB)
Clinical Trials
- Clinical Trials
Pharmacoeconomics
- Manufacturers
- Hoffmann la roche inc
- Bedford laboratories
- Luitpold pharmaceuticals inc
- Meda pharmaceuticals inc
- Apotex inc etobicoke site
- Aurobindo pharma ltd
- Hetero drugs ltd
- Par pharmaceutical inc
- Pliva pharmaceutical industry inc
- Roxane laboratories inc
- Sun pharmaceutical industries ltd
- Teva pharmaceuticals usa inc
- Packagers
- American Regent
- Apotex Inc.
- Aurobindo Pharma Ltd.
- Camber Pharmaceuticals Inc.
- Cardinal Health
- Diversified Healthcare Services Inc.
- F Hoffmann-La Roche Ltd.
- General Injectables and Vaccines Inc.
- Greenstone LLC
- Heartland Repack Services LLC
- Hetero Drugs Ltd.
- Ivax Pharmaceuticals
- Mckesson Corp.
- Meda AB
- Murfreesboro Pharmaceutical Nursing Supply
- Neuman Distributors Inc.
- Palmetto Pharmaceuticals Inc.
- Par Pharmaceuticals
- Physicians Total Care Inc.
- Pliva Inc.
- Preferred Pharmaceuticals Inc.
- Prepak Systems Inc.
- Resource Optimization and Innovation LLC
- Roxane Labs
- Sun Pharmaceutical Industries Ltd.
- Teva Pharmaceutical Industries Ltd.
- UDL Laboratories
- Vangard Labs Inc.
- Dosage forms
Form Route Strength Injection, solution Intravenous 10 mg/1mL Tablet Oral 10 mg/1 Tablet Oral 100 mg/1 Tablet Oral 20 mg/1 Tablet Oral 5 mg/1 Liquid Intravenous 10 mg Tablet Oral 100 mg Tablet Oral 10 mg Tablet Oral 20 mg Tablet Oral 5 mg - Prices
Unit description Cost Unit Demadex 100 mg tablet 5.69USD tablet Torsemide 100 mg tablet 3.16USD tablet Demadex 20 mg tablet 1.59USD tablet Demadex 10 mg tablet 1.39USD tablet Demadex 5 mg tablet 1.28USD tablet Torsemide 20 mg tablet 0.85USD tablet Torsemide 10 mg tablet 0.73USD tablet Torsemide 5 mg tablet 0.66USD tablet DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 164-164 °C Not Available water solubility Water soluble Not Available logP 2.3 Not Available pKa 7.1 Not Available - Predicted Properties
Property Value Source Water Solubility 0.0596 mg/mL ALOGPS logP 1.76 ALOGPS logP 1.86 ChemAxon logS -3.8 ALOGPS pKa (Strongest Acidic) 5.92 ChemAxon pKa (Strongest Basic) 4.2 ChemAxon Physiological Charge -1 ChemAxon Hydrogen Acceptor Count 5 ChemAxon Hydrogen Donor Count 3 ChemAxon Polar Surface Area 100.19 Å2 ChemAxon Rotatable Bond Count 4 ChemAxon Refractivity 91.89 m3·mol-1 ChemAxon Polarizability 36.15 Å3 ChemAxon Number of Rings 2 ChemAxon Bioavailability 1 ChemAxon Rule of Five Yes ChemAxon Ghose Filter Yes ChemAxon Veber's Rule No ChemAxon MDDR-like Rule No ChemAxon - Predicted ADMET features
Property Value Probability Human Intestinal Absorption + 0.9156 Blood Brain Barrier + 0.6871 Caco-2 permeable - 0.5374 P-glycoprotein substrate Non-substrate 0.799 P-glycoprotein inhibitor I Non-inhibitor 0.7695 P-glycoprotein inhibitor II Non-inhibitor 0.8232 Renal organic cation transporter Non-inhibitor 0.9185 CYP450 2C9 substrate Substrate 0.6049 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Non-substrate 0.7558 CYP450 1A2 substrate Non-inhibitor 0.9045 CYP450 2C9 inhibitor Non-inhibitor 0.6692 CYP450 2D6 inhibitor Non-inhibitor 0.923 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Inhibitor 0.5905 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.6324 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.8366 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 1.8740 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9854 hERG inhibition (predictor II) Non-inhibitor 0.8668
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Taxonomy
- Description
- This compound belongs to the class of organic compounds known as pyridinesulfonamides. These are heterocyclic compounds containing a pyridine ring substituted by one or more sulfonamide groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Pyridines and derivatives
- Sub Class
- Pyridinesulfonamides
- Direct Parent
- Pyridinesulfonamides
- Alternative Parents
- Toluenes / Sulfonylureas / Dihydropyridines / Secondary ketimines / Organosulfonic acids and derivatives / Heteroaromatic compounds / Aminosulfonyl compounds / Propargyl-type 1,3-dipolar organic compounds / Carboximidic acids and derivatives / Azacyclic compounds show 4 more
- Substituents
- Pyridine-3-sulfonamide / Dihydropyridine / Toluene / Sulfonylurea / Monocyclic benzene moiety / Hydropyridine / Benzenoid / Secondary ketimine / Heteroaromatic compound / Organic sulfonic acid or derivatives show 16 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- secondary amino compound, aminopyridine, N-sulfonylurea (CHEBI:9637)
Targets
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Sodium:potassium:chloride symporter activity
- Specific Function
- Electrically silent transporter system. Mediates sodium and chloride reabsorption. Plays a vital role in the regulation of ionic balance and cell volume.
- Gene Name
- SLC12A1
- Uniprot ID
- Q13621
- Uniprot Name
- Solute carrier family 12 member 1
- Molecular Weight
- 121449.13 Da
References
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
- Vormfelde SV, Sehrt D, Toliat MR, Schirmer M, Meineke I, Tzvetkov M, Nurnberg P, Brockmoller J: Genetic variation in the renal sodium transporters NKCC2, NCC, and ENaC in relation to the effects of loop diuretic drugs. Clin Pharmacol Ther. 2007 Sep;82(3):300-9. Epub 2007 Apr 25. [PubMed:17460608]
- Fortuno A, Muniz P, Ravassa S, Rodriguez JA, Fortuno MA, Zalba G, Diez J: Torasemide inhibits angiotensin II-induced vasoconstriction and intracellular calcium increase in the aorta of spontaneously hypertensive rats. Hypertension. 1999 Jul;34(1):138-43. [PubMed:10406837]
Enzymes
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
- Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
- Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
- Kind
- Protein
- Organism
- Human
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
- Gene Name
- PTGS1
- Uniprot ID
- P23219
- Uniprot Name
- Prostaglandin G/H synthase 1
- Molecular Weight
- 68685.82 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 12:44