Identification
- Summary
Warfarin is a vitamin K antagonist used to treat venous thromboembolism, pulmonary embolism, thromboembolism with atrial fibrillation, thromboembolism with cardiac valve replacement, and thromboembolic events post myocardial infarction.
- Brand Names
- Coumadin, Jantoven
- Generic Name
- Warfarin
- DrugBank Accession Number
- DB00682
- Background
Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Although originally marketed as a pesticide (d-Con, Rodex, among others), Warfarin has since become the most frequently prescribed oral anticoagulant in North America. Warfarin has several properties that should be noted when used medicinally, including its ability to cross the placental barrier during pregnancy which can result in fetal bleeding, spontaneous abortion, preterm birth, stillbirth, and neonatal death. Additional adverse effects such as necrosis, purple toe syndrome, osteoporosis, valve and artery calcification, and drug interactions have also been documented with warfarin use. Warfarin does not actually affect blood viscosity, rather, it inhibits vitamin-k dependent synthesis of biologically active forms of various clotting factors in addition to several regulatory factors.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Warfarin (DB00682)
- Weight
- Average: 308.3279
Monoisotopic: 308.104859 - Chemical Formula
- C19H16O4
- Synonyms
- 4-Hydroxy-3-(3-oxo-1-phenylbutyl)coumarin
- Coumafene
- Warfarin
- Warfarina
- Zoocoumarin
Pharmacology
- Indication
-
1) Prophylaxis and treatment of venous thromboembolism and related pulmonary embolism.
2) Prophylaxis and treatment of thromboembolism associated with atrial fibrillation.
3) Prophylaxis and treatment of thromboembolism associated with cardiac valve replacement.
4) Use as adjunct therapy to reduce mortality, recurrent myocardial infarction, and thromboembolic events post myocardial infarction.
Off-label uses include:
1) Secondary prevention of stroke and transient ischemic attacks in patients with rheumatic mitral valve disease but without atrial fibrillation.10
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in prevention of Mi •••••••••••• ••••••• •• •• Treatment of Pulmonary embolism •••••••••••• Prophylaxis of Pulmonary embolism •••••••••••• Adjunct therapy in prevention of Stroke •••••••••••• ••••••• •• •• Adjunct therapy in prevention of Systemic embolism •••••••••••• ••••••• •• •• - Contraindications & Blackbox Warnings
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Warfarin is an anticoagulant, as such it disrupts the coagulation cascade to reduce frequency and extent of thrombus formation.Label,17 In patients with deep vein thrombosis or atrial fibrillation there is an increased risk of thrombus formation due to the reduced movement of blood.15 For patients with cardiac valve disease or valve replacements this increased coagulability is due to tissue damage. Thrombi due to venous thrombosis can travel to the lungs and become pulmonary emboli, blocking circulation to a portion of lung tissue. Thrombi which form in the heart can travel to the brain and cause ischemic strokes. Prevention of these events is the primary goal of warfarin therapy.
Limitation of thrombus formation is also a source of adverse effects. In patients with atheroscelotic plaques rupture typically results in thrombus formation.11 When these patients are anticoagulated plaque rupture can allow the escape of cholesterol from the lipid core in the form of atheroemboli or cholesterol microemboli. These emboli are smaller than thrombi and block smaller vessels, usually less than 200 μm in diameter. The consequences of this are varied and depend on the location of the blockage. Effects include visual disturbances, acute kidney injury or worsening of chronic kidney disease, central nervous system ischemia, and purple or blue toe syndrome.Label,11 Blue toe syndrome can be reversed if it has not progressed to tissue necrosis but the other effects of microemboli are often permanent.
Antocoagulation appears to mediate warfarin-related nephropathy, a seemingly spontaneous kidney injury or worsening of chronic kidney disease associated with warfarin therapy.12 Nephropathy in this case appears to be due to increased passage of red blood cells through the glomerulus and subsequent blockage of renal tubules with red blood cell casts. This is worsened or possibly triggered by pre-existing kidney damage. Increased risk of warfarin-related nephropathy occurs at INRs over 3.0 but risk does not increase as a function of INR beyond this point.
Warfarin has been linked to the development of calciphylaxis.Label This is thought to be due to warfarin's inhibition of vitamin K recycling as VKA is needed for the carboxylation of matrix Gla protein.13 This protein is an anti-calcification factor and its inhibition through preventing the carboxylation step in its production leads to a shift in calcification balance in favor of calciphylaxis.
Tissue necrosis can occur early on in warfarin therapy.Label This is attributable to half lives of the clotting factors impacted by inhibition of vitamin K recycling.Label,14 Proteins C and S are anticoagulation factors with half lives of 8 and 24 hours respectively. The coagulation factors IX, X, VII, and thrombin (factor II) have half lives of 24, 36, 6, and 50 hours respectively. This means proteins C and S are inactivated sooner than pro-coagulation proteins, with the exception of factor VII, resulting in a pro-thrombotic state for the first few days of therapy. Thrombi which form in this time period can occlude arterioles in various locations, blocking blood flow and causing tissue necrosis due to ischemia.
- Mechanism of action
Warfarin is a [vitamin K] antagonist which acts to inhibit the production of vitamin K by vitamin K epoxide reductase.Label,14,16 The reduced form of vitamin K, vitamin KH2 is a cofactor used in the γ-carboxylation of coagulation factors VII, IX, X, and thrombin. Carboxylation induces a conformational change allowing the factors to bind Ca2+ and to phospholipid surfaces. Uncarboxylated factors VII, IX, X, and thrombin are biologically inactive and therefore serve to interrupt the coagulation cascade. The endogenous anticoagulation proteins C and S also require γ-carboxylation to function. This is particularly true in the case of thrombin which must be activated in order to form a thrombus. vitamin KH2 is converted to vitamin K epoxide as part of the γ-carboxylation reaction catalyzed by γ-glutamyl carboxylase. Vitamin K epoxide is then converted to vitamin K1 by vitamin K epoxide reductase then back to vitamin KH2 by vitamin K reductase. Warfarin binds to vitamin K epoxide reductase complex subunit 1 and irreversibly inhibits the enzyme thereby stopping the recycling of vitamin K by preventing the conversion of vitamin K epoxide to vitamin K1. This process creates a hypercoagulable state for a short time as proteins C and S degrade first with half lives of 8 and 24 hours, with the exception of factor VII which has a half life of 6 hours.14 Factors IX, X, and finally thrombin degrade later with half lives of 24, 36, and 50 hours resulting in a dominant anticoagulation effect.14 In order to reverse this anticoagulation vitamin K must be supplied, either exogenously or by removal of the vitamin K epoxide reductase inhibition, and time allowed for new coagulation factors to be synthesized.Label,14,16 It takes approximately 2 days for new coagulation factors to be synthesized in the liver. Vitamin K2, functionally identical to vitamin K1, is synthesized by gut bacteria leading to interactions with antibiotics as elimination of these bacteria can reduce vitamin K216
Target Actions Organism AVitamin K epoxide reductase complex subunit 1 inhibitorHumans UNuclear receptor subfamily 1 group I member 2 Not Available Humans - Absorption
Completely absorbed from the GI tract. The mean Tmax for warfarin sodium tablets is 4 hours.Label,17,9
- Volume of distribution
Vd of 0.14 L/kg.Label,17,9 Warfarin has a distrubution phase lasting 6-12 hours.17 It is known to cross the placenta and achieves fetal serum concentrations similar to maternal concentrations.
- Protein binding
- Metabolism
Metabolism of warfarin is both stereo- and regio-selective.9 The major metabolic pathway is oxidation to various hydroxywarfarins, comprising 80-85% of the total metabolites. CYP2C9 is the major enzyme catalyzing the 6- and 7-hydroxylation of S-warfarin while 4'-hydroxylation occurs through CYP2C18 with minor contributions from CYP2C19. R-warfarin is metabolized to 4'-hydroxywarfarin by CYP2C8 with some contirbuting by CYP2C19, 6- and 8-hydroxywarfarin by CYP1A2 and CYP2C19, 7-hydroxywarfarin by CYP1A2 and CYP2C8, and lastly to 10-hydroxywarfarin by CYP3A4. The 10-hydroxywarfarin metabolite as well as a benzylic alcohol metabolite undergo an elimination step to form dehydrowarfarin. The minor pathway of metabolism is the reduction of the ketone group to warfarin alcohols, comprising 20% of the metabolites. Limited conjugation occurs with sulfate and gluronic acid groups but these metabolites have only been confirmed for R-hydroxywarfarins.
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- Route of elimination
The elimination of warfarin is almost entirely by metabolism with a small amount excreted unchanged.Label,17,9 80% of the total dose is excreted in the urine with the remaining 20% appearing in the feces.9
- Half-life
R-warfarin is cleared more slowly than S-warfarin, at about half the rate.Label T1/2 for R-warfarin is 37-89 hours. T1/2 for S-warfarin is 21-43 hours.
- Clearance
Clearance of warfarin varies depending on CYP2C9 genotype.Label,17 The *2 and *3 alleles appear in the Caucasian population at frequencies of 11% and 7% and are known to reduce clearance warfarin. Additional clearance reducing genotypes include the *5, *6, *9 and *11 alleles. Genotypes for which population clearance estimates have been found are listed below.
*1/*1 = 0.065 mL/min/kg
*1/*2, *1/*3 = 0.041 mL/min/kg
*2/*2, *2/*3, *3/*3 = 0.020 mg/min/kg
- Adverse Effects
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LD50 Values
Mouse: 3 mg/kg (Oral), 165 mg/kg (IV), 750 mg/kg (IP)18
Rat: 1.6 mg/kg (Oral), 320 mg/kg (Inhaled), 1400 mg/kg (Skin)18
Rabbit: 800 mg/kg (Oral)18
Pig: 1 mg/kg (Oral)18
Dog: 3 mg/kg (Oral)18
Cat: 6 mg/kg (Oral)18
Chicken: 942 mg/kg (Oral)18
Guinea Pig: 180 mg/kg (Oral)18
Overdose
Doses of 1-2 mg/kg/day over a period of 15 days have been fatal in humans.19 Warfarin overdose is primarily associated with major bleeding particularly from the mucous membranes, gastrointestinal tract, and genitourinary system.Label,19 Epistaxis, ecchymoses, as well as renal and hepatic bleeding are also associated. These symptoms become apparent within 2-4 days of overdose although increases in prothrombin time can be observed within 24 hours. Treatment for overdosed patients includes discontinuation of warfarin and administration of [vitamin K]. For more urgent reversal of anticoagulation prothrombin complex concentrate, blood plasma, or coagulation factor VIIa infusion can be used.Label Patients can be safely re-anticoagulated after reversal of the overdose.
Carcinogenicity & Mutagenicity
The carcinogenicity and mutagenicity of warfarin have not been thoroughly investigated.Label
Reproductive Toxicity
Warfarin is known to be a teratogen and its use during pregnancy is contraindicated in the absence of high thrombotic risk.Label,19 Fetal warfarin syndrome, attributed to exposure during the 1st trimester, is characterized by nasal hypoplasia with or without stippled epiphyses, possible failure of nasal septum development, and low birth weight. Either dorsal midline dysplasia or ventral midline dysplasia can occur. Dorsal midline dysplasia includes agenisis of the corpus callosum, Dandy-Walker malformations, midline cerebellar hypoplasia. Ventral midline dysplasia is characterized by eye anomalies which can potentially include optic atrophy, blindness, and microphthalmia. Exposure during the 2nd and 3rd trimester is associated with hypoplasia of the extremities, developmental retardation, microcephaly, hydrocephaly, schizencephaly, seizures, scoliosis, deafness, congenital heart malformations, and fetal death. The critical exposure period is estimated to be week 6-9 based on case reports. Effects noted in the Canadian product monograph include developing a single kidney, asplenia, anencephaly, spina bifida, cranial nerve palsy, polydactyl malformations, corneal leukoma, diaphragm hernia, and cleft palate.17
Lactation
Official product monographs mention a study in 15 women.Label,17 Warfarin was not detected in the breast milk of any woman and 6 infants were documented as having normal prothrombin times. The remaining 9 infants were not tested. Another study in 13 women using doses of 2-12 mg also revealed no detectable warfarin in breast milk.20 A woman who mistakenly took 25 mg of warfarin for 7 days while breastfeeding presented to an emergency room with an INR of 10 and prothrombin time of over 100 s. Her infant had a normal INR of 1.0 and prothrombin time of 10.3. The infant in this case has an increased prothrombin time of 33.8 s three weeks previous but this was judged not to be due to warfarin exposure.
- Pathways
Pathway Category Warfarin Action Pathway Drug action - Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C9 CYP2C9*2 (T;T) / (C;T) T Allele Effect Directly Studied Patients with this genotype have reduced metabolism of warfarin. Details Vitamin K epoxide reductase complex subunit 1 --- (A;A) / (A;G) -1639G>A Effect Directly Studied Patients with this genotype in VKORC1 are associated with reduced metabolism of warfarin and increased risk of serious bleeding thus require lower doses. Details Phylloquinone omega-hydroxylase CYP4F2 --- (T;T) T Allele, homozygous Effect Directly Studied Patients with this genotype in CP4F2 may require higer doses of warfarin to attain therapeutic anticoagulant activity. Details Cytochrome P450 2C9 CYP2C9*2 (T;T) / (C;T) T Allele Effect Directly Studied The presence of this polymorphism in CYP2C9 is associated with reduction in warfarin metabolism. Details Cytochrome P450 2C9 CYP2C9*3 (C;C) / (A;C) C Allele Effect Directly Studied The presence of this polymorphism in CYP2C9 is associated with reduction in warfarin metabolism. Details Cytochrome P450 2C9 CYP2C9*4 Not Available 1076T>C Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*5 Not Available 1080C>G Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*8 Not Available 449G>A Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*11 Not Available 1003C>T Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*12 Not Available 1465C>T Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*13 Not Available 269T>C Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*14 Not Available 374G>A Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*16 Not Available 895A>G Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*18 Not Available 1075A>C / 1190A>C … show all Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*26 Not Available 389C>G Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*28 Not Available 641A>T Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*30 Not Available 1429G>A Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*33 Not Available 395G>A Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*6 Not Available 818delA Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*15 Not Available 485C>A Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*25 Not Available 353_362delAGAAATGGAA Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*35 Not Available 374G>T / 430C>T Effect Inferred Poor drug metabolizer, lower dose recommended. Details Cytochrome P450 2C9 CYP2C9*6 Not Available 818delA Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*15 Not Available 485C>A Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*25 Not Available 353_362delAGAAATGGAA Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*35 Not Available 374G>T / 430C>T Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*3 Not Available 1075A>C Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*4 Not Available 1076T>C Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*5 Not Available 1080C>G Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*8 Not Available 449G>A Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*11 Not Available 1003C>T Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*12 Not Available 1465C>T Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*13 Not Available 269T>C Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*14 Not Available 374G>A Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*16 Not Available 895A>G Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*18 Not Available 1075A>C / 1190A>C … show all Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*26 Not Available 389C>G Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*28 Not Available 641A>T Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*30 Not Available 1429G>A Effect Inferred Poor drug metabolizer, lower dose requirements Details Cytochrome P450 2C9 CYP2C9*33 Not Available 395G>A Effect Inferred Poor drug metabolizer, lower dose requirements Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Warfarin which could result in a higher serum level. Abametapir The serum concentration of Warfarin can be increased when it is combined with Abametapir. Abatacept The metabolism of Warfarin can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Warfarin. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Warfarin. - Food Interactions
- Avoid drastic dietary changes.
- Avoid foods rich in vitamin K. Vitamin K in foods such as leafy vegetables can reduce warfarin efficacy.
- Avoid grapefruit products. They may interfere with warfarin metabolism and increase INR, increasing the risk of bleeding.
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Avoid St. John's Wort. This drug may reduce warfarin efficacy.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Warfarin potassium I47IU4FOCO 2610-86-8 WSHYKIAQCMIPTB-UHFFFAOYSA-M Warfarin sodium 6153CWM0CL 129-06-6 KYITYFHKDODNCQ-UHFFFAOYSA-M - Product Images
- International/Other Brands
- Lawarin / Marevan / Waran / Warfant
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Coumadin Tablet 3 mg/1 Oral Aphena Pharma Solutions Tennessee, Inc. 2009-01-01 Not applicable US 
Coumadin Tablet 5 mg/1 Oral Aphena Pharma Solutions - Tennessee, Inc. 2009-01-01 2019-02-26 US Coumadin Tablet 1 mg/1 Oral Bristol-Myers Squibb Pharma Company 2009-01-01 2020-11-30 US 
Coumadin Injection, powder, lyophilized, for solution 2 mg/1mL Intravenous Bristol Myers Squibb Holdings Pharma, Ltd. Liability Company 2009-01-01 2016-11-30 US Coumadin Tablet 5 mg/1 Oral Remedy Repack 2012-07-19 2013-08-27 US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Apo-warfarin Tablet 5 mg Oral Apotex Corporation 2000-10-16 Not applicable Canada 
Apo-warfarin Tablet 2 mg Oral Apotex Corporation 2000-10-16 Not applicable Canada Apo-warfarin Tablet 3 mg Oral Apotex Corporation 2002-04-23 Not applicable Canada Apo-warfarin Tablet 4 mg Oral Apotex Corporation 2000-10-16 Not applicable Canada Apo-warfarin Tablet 1 mg Oral Apotex Corporation 2000-10-16 Not applicable Canada - Over the Counter Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image มาฟอแรน 4 มก. Tablet 4 mg Oral บริษัท เภสัชกรรมศรีประสิทธิ์ จำกัด จำกัด 2003-03-17 Not applicable Thailand 
Categories
- ATC Codes
- B01AA03 — Warfarin
- Drug Categories
- 4-Hydroxycoumarins
- Agrochemicals
- Anticoagulants
- Blood and Blood Forming Organs
- Compounds used in a research, industrial, or household setting
- Coumarins
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C18 Substrates
- Cytochrome P-450 CYP2C18 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C9 Inducers
- Cytochrome P-450 CYP2C9 Inducers (weak)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Drugs that are Mainly Renally Excreted with a Narrow Therapeutic Index
- Hematologic Agents
- Heterocyclic Compounds, Fused-Ring
- Narrow Therapeutic Index Drugs
- Pesticides
- Pyrans
- Rodenticides
- Toxic Actions
- Vitamin K Antagonists
- Vitamin K Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 4-hydroxycoumarins. These are coumarins that contain one or more hydroxyl groups attached to C4-position the coumarin skeleton.
- Kingdom
- Organic compounds
- Super Class
- Phenylpropanoids and polyketides
- Class
- Coumarins and derivatives
- Sub Class
- Hydroxycoumarins
- Direct Parent
- 4-hydroxycoumarins
- Alternative Parents
- 1-benzopyrans / Pyranones and derivatives / Benzene and substituted derivatives / Vinylogous acids / Heteroaromatic compounds / Lactones / Ketones / Oxacyclic compounds / Organic oxides / Hydrocarbon derivatives
- Substituents
- 1-benzopyran / 4-hydroxycoumarin / Aromatic heteropolycyclic compound / Benzenoid / Benzopyran / Carbonyl group / Heteroaromatic compound / Hydrocarbon derivative / Ketone / Lactone
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- methyl ketone, hydroxycoumarin (CHEBI:87732) / Coumarin rodenticides (C01541)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 5Q7ZVV76EI
- CAS number
- 81-81-2
- InChI Key
- PJVWKTKQMONHTI-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H16O4/c1-12(20)11-15(13-7-3-2-4-8-13)17-18(21)14-9-5-6-10-16(14)23-19(17)22/h2-10,15,21H,11H2,1H3
- IUPAC Name
- 4-hydroxy-3-(3-oxo-1-phenylbutyl)-2H-chromen-2-one
- SMILES
- CC(=O)CC(C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2
References
- Synthesis Reference
Nasri W. Badran, "Microcrystalline 3-(alpha-acetonylbenzyl)-4-hydroxycoumarin (warfarin) and methods of making." U.S. Patent US4113744, issued April, 1960.
US4113744- General References
- Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E: The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):204S-233S. [Article]
- Whitlon DS, Sadowski JA, Suttie JW: Mechanism of coumarin action: significance of vitamin K epoxide reductase inhibition. Biochemistry. 1978 Apr 18;17(8):1371-7. [Article]
- Li T, Chang CY, Jin DY, Lin PJ, Khvorova A, Stafford DW: Identification of the gene for vitamin K epoxide reductase. Nature. 2004 Feb 5;427(6974):541-4. [Article]
- Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, Muller CR, Strom TM, Oldenburg J: Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. [Article]
- Hirsh J, Fuster V, Ansell J, Halperin JL: American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol. 2003 May 7;41(9):1633-52. [Article]
- Holbrook AM, Pereira JA, Labiris R, McDonald H, Douketis JD, Crowther M, Wells PS: Systematic overview of warfarin and its drug and food interactions. Arch Intern Med. 2005 May 23;165(10):1095-106. [Article]
- Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G: Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):160S-198S. doi: 10.1378/chest.08-0670. [Article]
- Freedman MD: Oral anticoagulants: pharmacodynamics, clinical indications and adverse effects. J Clin Pharmacol. 1992 Mar;32(3):196-209. [Article]
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD, Fang MC, Fisher M, Furie KL, Heck DV, Johnston SC, Kasner SE, Kittner SJ, Mitchell PH, Rich MW, Richardson D, Schwamm LH, Wilson JA: Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014 Jul;45(7):2160-236. doi: 10.1161/STR.0000000000000024. Epub 2014 May 1. [Article]
- Saric M, Kronzon I: Aortic atherosclerosis and embolic events. Curr Cardiol Rep. 2012 Jun;14(3):342-9. doi: 10.1007/s11886-012-0261-2. [Article]
- Brodsky SV: Anticoagulants and acute kidney injury: clinical and pathology considerations. Kidney Res Clin Pract. 2014 Dec;33(4):174-80. doi: 10.1016/j.krcp.2014.11.001. Epub 2014 Nov 18. [Article]
- Portales-Castillo I, Kroshinsky D, Malhotra CK, Culber-Costley R, Cozzolino MG, Karparis S, Halasz CL, Goverman J, Manley HJ, Malhotra R, Nigwekar SU: Calciphylaxis-as a drug induced adverse event. Expert Opin Drug Saf. 2019 Jan;18(1):29-35. doi: 10.1080/14740338.2019.1559813. Epub 2018 Dec 24. [Article]
- Fawzy AM, Lip GYH: Pharmacokinetics and pharmacodynamics of oral anticoagulants used in atrial fibrillation. Expert Opin Drug Metab Toxicol. 2019 May;15(5):381-398. doi: 10.1080/17425255.2019.1604686. Epub 2019 Apr 19. [Article]
- Aster JC, Bunn HF (2017). Pathophysiology of Blood Disorders (2nd ed.). McGraw-Hill.
- Brunton LL, Hilal-Dandan R, Knollmann BC. eds (2018). Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
- Warfarin DPD Monograph [Link]
- ChemIDplus: Warfarin [Link]
- HSDB: Warfarin [Link]
- LactMed: Warfarin [Link]
- FDA Approved Drug Products: COUMADIN (warfarin sodium) [Link]
- DailyMed: Warfarin sodium tablets for oral use [Link]
- External Links
- Human Metabolome Database
- HMDB0001935
- KEGG Compound
- C01541
- PubChem Compound
- 54678486
- PubChem Substance
- 46504711
- ChemSpider
- 10442445
- BindingDB
- 50343352
- 11289
- ChEBI
- 87732
- ChEMBL
- CHEMBL1464
- Therapeutic Targets Database
- DAP000770
- PharmGKB
- PA451906
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Warfarin
- FDA label
- Download (641 KB)
- MSDS
- Download (59.5 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Not Available Drug Therapy, Combination 1 4 Completed Not Available Healthy Subjects (HS) 1 4 Completed Other Cerebral Ischemic Events / Cognitive Dysfunctions / Dementia 1 4 Completed Other Coagulation Disorder 1 4 Completed Other Post-operative Atrial Fibrillation (POAF) 1
Pharmacoeconomics
- Manufacturers
- Pharmaceutical research assoc inc
- Bristol myers squibb pharma co
- Usl pharma inc
- Abbott laboratories pharmaceutical products div
- Barr laboratories inc
- Mylan pharmaceuticals inc
- Pliva inc
- Sandoz inc
- Taro pharmaceuticals inc
- Watson laboratories inc
- Zydus pharmaceuticals usa inc
- Packagers
- Advanced Pharmaceutical Services Inc.
- Amerisource Health Services Corp.
- Apothecon
- AQ Pharmaceuticals Inc.
- A-S Medication Solutions LLC
- Atlantic Biologicals Corporation
- Barr Pharmaceuticals
- Blenheim Pharmacal
- Bristol-Myers Squibb Co.
- Cadila Healthcare Ltd.
- Cardinal Health
- Caremark LLC
- Coastal Family Health Center Inc.
- Dept Health Central Pharmacy
- Direct Dispensing Inc.
- Dispensing Solutions
- Diversified Healthcare Services Inc.
- Genpharm LP
- Heartland Repack Services LLC
- Ipca Laboratories Ltd.
- Kaiser Foundation Hospital
- Lake Erie Medical and Surgical Supply
- Mallinckrodt Inc.
- Murfreesboro Pharmaceutical Nursing Supply
- Mylan
- Neuman Distributors Inc.
- Nucare Pharmaceuticals Inc.
- Palmetto Pharmaceuticals Inc.
- PCA LLC
- PD-Rx Pharmaceuticals Inc.
- Pharmaceutical Utilization Management Program VA Inc.
- Pharmedix
- Physicians Total Care Inc.
- Pliva Inc.
- Prepackage Specialists
- Prepak Systems Inc.
- Rebel Distributors Corp.
- Remedy Repack
- Resource Optimization and Innovation LLC
- Sandhills Packaging Inc.
- Southwood Pharmaceuticals
- Spectrum Pharmaceuticals
- St Mary's Medical Park Pharmacy
- Stat Scripts LLC
- Taro Pharmaceuticals USA
- Tya Pharmaceuticals
- Upsher Smith Laboratories
- USL Pharma Inc.
- Va Cmop Dallas
- Vangard Labs Inc.
- Zydus Pharmaceuticals
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 2 mg/1mL Powder, for solution Intravenous 5 mg / vial Tablet Oral 10 mg Tablet Oral 2.5 mg Tablet Oral 6 mg Tablet Oral 5.000 mg Tablet Oral 10.0 mg Tablet Oral 3.0 mg Tablet Oral 4.0 mg Tablet Oral 5.0 mg Tablet Oral 7.5 mg Tablet Oral 1 mg/1 Tablet Oral 10 mg/1 Tablet Oral 2 mg/1 Tablet Oral 2.5 mg/1 Tablet Oral 3 mg/1 Tablet Oral 4 mg/1 Tablet Oral 5 mg/1 Tablet Oral 6 mg/1 Tablet Oral 7.5 mg/1 Tablet Oral 7.5 ug/1 Tablet Oral Tablet, delayed release Oral 5 mg Tablet, film coated Oral 5 mg Tablet Oral 5 mg / tab Tablet Oral 1 mg Tablet Oral 3 mg Tablet Oral 4 mg Tablet Oral 2 mg Tablet Oral 5 mg - Prices
Unit description Cost Unit Warfarin sodium powder 54.53USD g Coumadin 5 mg vial 34.07USD vial Coumadin 10 mg tablet 2.01USD tablet Coumadin 7.5 mg tablet 1.97USD tablet Coumadin 6 mg tablet 1.94USD tablet Coumadin 3 mg tablet 1.51USD tablet Coumadin 5 mg tablet 1.51USD tablet Coumadin 4 mg tablet 1.49USD tablet Coumadin 2.5 mg tablet 1.46USD tablet Coumadin 2 mg tablet 1.4USD tablet Coumadin 1 mg tablet 1.37USD tablet Warfarin sodium 10 mg tablet 1.0USD tablet Warfarin sodium 7.5 mg tablet 0.96USD tablet Jantoven 10 mg tablet 0.76USD tablet Jantoven 7.5 mg tablet 0.74USD tablet Jantoven 6 mg tablet 0.72USD tablet Warfarin sodium 6 mg tablet 0.68USD tablet Warfarin sodium 3 mg tablet 0.66USD tablet Warfarin sodium 4 mg tablet 0.66USD tablet Warfarin sodium 2.5 mg tablet 0.65USD tablet Warfarin sodium 5 mg tablet 0.65USD tablet Warfarin sodium 2 mg tablet 0.63USD tablet Warfarin sodium 1 mg tablet 0.61USD tablet Jantoven 5 mg tablet 0.59USD tablet Jantoven 2 mg tablet 0.56USD tablet Jantoven 4 mg tablet 0.56USD tablet Jantoven 2.5 mg tablet 0.53USD tablet Jantoven 3 mg tablet 0.53USD tablet Coumadin 10 mg Tablet 0.5USD tablet Jantoven 1 mg tablet 0.49USD tablet Coumadin 3 mg Tablet 0.43USD tablet Coumadin 4 mg Tablet 0.43USD tablet Coumadin 2 mg Tablet 0.35USD tablet Coumadin 1 mg Tablet 0.33USD tablet Taro-Warfarin 7.5 mg Tablet 0.33USD tablet Taro-Warfarin 6 mg Tablet 0.31USD tablet Apo-Warfarin 10 mg Tablet 0.28USD tablet Coumadin 2.5 mg Tablet 0.28USD tablet Coumadin 5 mg Tablet 0.28USD tablet Mylan-Warfarin 10 mg Tablet 0.28USD tablet Taro-Warfarin 10 mg Tablet 0.28USD tablet Warfarin 10 mg Tablet 0.28USD tablet Apo-Warfarin 3 mg Tablet 0.24USD tablet Apo-Warfarin 4 mg Tablet 0.24USD tablet Mylan-Warfarin 3 mg Tablet 0.24USD tablet Mylan-Warfarin 4 mg Tablet 0.24USD tablet Novo-Warfarin 3 mg Tablet 0.24USD tablet Novo-Warfarin 4 mg Tablet 0.24USD tablet Taro-Warfarin 3 mg Tablet 0.24USD tablet Taro-Warfarin 4 mg Tablet 0.24USD tablet Warfarin 3 mg Tablet 0.24USD tablet Warfarin 4 mg Tablet 0.24USD tablet Apo-Warfarin 2 mg Tablet 0.19USD tablet Mylan-Warfarin 2 mg Tablet 0.19USD tablet Novo-Warfarin 2 mg Tablet 0.19USD tablet Taro-Warfarin 2 mg Tablet 0.19USD tablet Warfarin 2 mg Tablet 0.19USD tablet Apo-Warfarin 1 mg Tablet 0.18USD tablet Mylan-Warfarin 1 mg Tablet 0.18USD tablet Novo-Warfarin 1 mg Tablet 0.18USD tablet Taro-Warfarin 1 mg Tablet 0.18USD tablet Warfarin 1 mg Tablet 0.18USD tablet Apo-Warfarin 5 mg Tablet 0.16USD tablet Mylan-Warfarin 5 mg Tablet 0.16USD tablet Novo-Warfarin 5 mg Tablet 0.16USD tablet Taro-Warfarin 5 mg Tablet 0.16USD tablet Warfarin 5 mg Tablet 0.16USD tablet Apo-Warfarin 2.5 mg Tablet 0.15USD tablet Mylan-Warfarin 2.5 mg Tablet 0.15USD tablet Novo-Warfarin 2.5 mg Tablet 0.15USD tablet Taro-Warfarin 2.5 mg Tablet 0.15USD tablet Warfarin 2.5 mg Tablet 0.15USD 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) 161 °C PhysProp water solubility 17 mg/L (at 20 °C) TOMLIN,C (1997) logP 2.70 HANSCH,C ET AL. (1995) logS -3.89 ADME Research, USCD Caco2 permeability -4.68 ADME Research, USCD pKa 5.0 UFER, M (2005) - Predicted Properties
Property Value Source Water Solubility 0.0472 mg/mL ALOGPS logP 2.41 ALOGPS logP 2.74 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 5.56 Chemaxon pKa (Strongest Basic) -6.9 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 63.6 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 86.86 m3·mol-1 Chemaxon Polarizability 31.9 Å3 Chemaxon Number of Rings 3 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 + 0.9109 Blood Brain Barrier + 0.9124 Caco-2 permeable + 0.8867 P-glycoprotein substrate Substrate 0.5502 P-glycoprotein inhibitor I Non-inhibitor 0.8782 P-glycoprotein inhibitor II Non-inhibitor 0.8382 Renal organic cation transporter Non-inhibitor 0.8863 CYP450 2C9 substrate Non-substrate 0.678 CYP450 2D6 substrate Substrate 0.5658 CYP450 3A4 substrate Non-substrate 0.6007 CYP450 1A2 substrate Non-inhibitor 0.714 CYP450 2C9 inhibitor Inhibitor 0.7657 CYP450 2D6 inhibitor Non-inhibitor 0.9286 CYP450 2C19 inhibitor Non-inhibitor 0.9161 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8785 Ames test Non AMES toxic 0.6844 Carcinogenicity Non-carcinogens 0.9352 Biodegradation Not ready biodegradable 0.7474 Rat acute toxicity 4.1700 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8768 hERG inhibition (predictor II) Non-inhibitor 0.9615
Spectra
- Mass Spec (NIST)
- Download (8.72 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.805281 predictedDarkChem Lite v0.1.0 [M-H]- 170.50896 predictedDeepCCS 1.0 (2019) [M+H]+ 185.111581 predictedDarkChem Lite v0.1.0 [M+H]+ 172.86697 predictedDeepCCS 1.0 (2019) [M+Na]+ 184.587381 predictedDarkChem Lite v0.1.0 [M+Na]+ 178.96011 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Vitamin-k-epoxide reductase (warfarin-sensitive) activity
- Specific Function
- Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the...
- Gene Name
- VKORC1
- Uniprot ID
- Q9BQB6
- Uniprot Name
- Vitamin K epoxide reductase complex subunit 1
- Molecular Weight
- 18234.3 Da
References
- Gebauer M: Synthesis and structure-activity relationships of novel warfarin derivatives. Bioorg Med Chem. 2007 Mar 15;15(6):2414-20. Epub 2007 Jan 17. [Article]
- Zhu Y, Shennan M, Reynolds KK, Johnson NA, Herrnberger MR, Valdes R Jr, Linder MW: Estimation of warfarin maintenance dose based on VKORC1 (-1639 G>A) and CYP2C9 genotypes. Clin Chem. 2007 Jul;53(7):1199-205. Epub 2007 May 17. [Article]
- Yin T, Miyata T: Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives. Thromb Res. 2007;120(1):1-10. Epub 2006 Dec 11. [Article]
- Osman A, Enstrom C, Lindahl TL: Plasma S/R ratio of warfarin co-varies with VKORC1 haplotype. Blood Coagul Fibrinolysis. 2007 Apr;18(3):293-6. [Article]
- Limdi NA, McGwin G, Goldstein JA, Beasley TM, Arnett DK, Adler BK, Baird MF, Acton RT: Influence of CYP2C9 and VKORC1 1173C/T genotype on the risk of hemorrhagic complications in African-American and European-American patients on warfarin. Clin Pharmacol Ther. 2008 Feb;83(2):312-21. Epub 2007 Jul 25. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Curator comments
- Only S-enantiomer results in activation.
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Rulcova A, Prokopova I, Krausova L, Bitman M, Vrzal R, Dvorak Z, Blahos J, Pavek P: Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. J Thromb Haemost. 2010 Dec;8(12):2708-17. doi: 10.1111/j.1538-7836.2010.04036.x. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- 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
- Daly AK, Rettie AE, Fowler DM, Miners JO: Pharmacogenomics of CYP2C9: Functional and Clinical Considerations. J Pers Med. 2017 Dec 28;8(1). pii: jpm8010001. doi: 10.3390/jpm8010001. [Article]
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Rulcova A, Prokopova I, Krausova L, Bitman M, Vrzal R, Dvorak Z, Blahos J, Pavek P: Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. J Thromb Haemost. 2010 Dec;8(12):2708-17. doi: 10.1111/j.1538-7836.2010.04036.x. [Article]
- Flockhart Table of Drug Interactions [Link]
- Warfarin FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 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. [Article]
- Fulco PP, Zingone MM, Higginson RT: Possible antiretroviral therapy-warfarin drug interaction. Pharmacotherapy. 2008 Jul;28(7):945-9. doi: 10.1592/phco.28.7.945. [Article]
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- FDA label warfarin [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 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. [Article]
- Brandon EF, Meijerman I, Klijn JS, den Arend D, Sparidans RW, Lazaro LL, Beijnen JH, Schellens JH: In-vitro cytotoxicity of ET-743 (Trabectedin, Yondelis), a marine anti-cancer drug, in the Hep G2 cell line: influence of cytochrome P450 and phase II inhibition, and cytochrome P450 induction. Anticancer Drugs. 2005 Oct;16(9):935-43. [Article]
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInducer
- General Function
- Vitamin d3 25-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 performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 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. [Article]
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Rulcova A, Prokopova I, Krausova L, Bitman M, Vrzal R, Dvorak Z, Blahos J, Pavek P: Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes. J Thromb Haemost. 2010 Dec;8(12):2708-17. doi: 10.1111/j.1538-7836.2010.04036.x. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- 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. [Article]
- Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Kind
- Protein
- Organism
- Humans
- 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
- CYP2C18
- Uniprot ID
- P33260
- Uniprot Name
- Cytochrome P450 2C18
- Molecular Weight
- 55710.075 Da
References
- Ufer M: Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46. [Article]
- Lee MT, Chen CH, Chou CH, Lu LS, Chuang HP, Chen YT, Saleem AN, Wen MS, Chen JJ, Wu JY, Chen YT: Genetic determinants of warfarin dosing in the Han-Chinese population. Pharmacogenomics. 2009 Dec;10(12):1905-13. doi: 10.2217/pgs.09.106. [Article]
- Wadelius M, Chen LY, Eriksson N, Bumpstead S, Ghori J, Wadelius C, Bentley D, McGinnis R, Deloukas P: Association of warfarin dose with genes involved in its action and metabolism. Hum Genet. 2007 Mar;121(1):23-34. doi: 10.1007/s00439-006-0260-8. Epub 2006 Oct 18. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- BinderRegulator
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Yamasaki K, Maruyama T, Kragh-Hansen U, Otagiri M: Characterization of site I on human serum albumin: concept about the structure of a drug binding site. Biochim Biophys Acta. 1996 Jul 18;1295(2):147-57. [Article]
- Joseph KS, Hage DS: The effects of glycation on the binding of human serum albumin to warfarin and L-tryptophan. J Pharm Biomed Anal. 2010 Nov 2;53(3):811-8. doi: 10.1016/j.jpba.2010.04.035. Epub 2010 May 6. [Article]
- Wybranowski T, Cyrankiewicz M, Ziomkowska B, Kruszewski S: The HSA affinity of warfarin and flurbiprofen determined by fluorescence anisotropy measurements of camptothecin. Biosystems. 2008 Dec;94(3):258-62. doi: 10.1016/j.biosystems.2008.05.034. Epub 2008 Jul 31. [Article]
- Bertucci C, Wainer IW: Improved chromatographic performance of a modified human albumin based stationary phase. Chirality. 1997;9(4):335-40. [Article]
- Watanabe H, Yamasaki K, Kragh-Hansen U, Tanase S, Harada K, Suenaga A, Otagiri M: In vitro and in vivo properties of recombinant human serum albumin from Pichia pastoris purified by a method of short processing time. Pharm Res. 2001 Dec;18(12):1775-81. doi: 10.1023/a:1013391001141. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- General Function
- Not Available
- Specific Function
- Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
- Gene Name
- ORM1
- Uniprot ID
- P02763
- Uniprot Name
- Alpha-1-acid glycoprotein 1
- Molecular Weight
- 23511.38 Da
References
- Hazai E, Visy J, Fitos I, Bikadi Z, Simonyi M: Selective binding of coumarin enantiomers to human alpha1-acid glycoprotein genetic variants. Bioorg Med Chem. 2006 Mar 15;14(6):1959-65. Epub 2005 Nov 15. [Article]
- Nakagawa T, Kishino S, Itoh S, Sugawara M, Miyazaki K: Differential binding of disopyramide and warfarin enantiomers to human alpha(1)-acid glycoprotein variants. Br J Clin Pharmacol. 2003 Dec;56(6):664-9. [Article]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:54