This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Identification
- Generic Name
- (R)-warfarin
- DrugBank Accession Number
- DB08496
- Background
Warfarin consists of a racemic mixture of two active enantiomers—R- and S- forms—each of which is cleared by different pathways. S-warfarin is 2-5 times more potent than the R-isomer in producing an anticoagulant response.3
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for (R)-warfarin (DB08496)
- Weight
- Average: 308.3279
Monoisotopic: 308.104859 - Chemical Formula
- C19H16O4
- Synonyms
- (+)-warfarin
- (R)-4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2-benzopyrone
- (R)-4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one
- 4-hydroxy-3-[(1R)-3-oxo-1-phenylbutyl]-2H-chromen-2-one
- R-warfarin
- R,R-Warfarin alcohol
Pharmacology
- Indication
Not Available
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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- Pharmacodynamics
Not Available
- Mechanism of action
- Not Available
- Absorption
Not Available
- Volume of distribution
The volume of distribution was 10.9L (95% confidence interval 8.63, 13.2), according to a study by Lane et al. 1
- Protein binding
Not Available
- Metabolism
Human liver cytochrome P450 enzymes involved in the 7-hydroxylation of R- and S-warfarin enantiomers.
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
0.125L/h, (95% confidence interval 0.115, 0.135) in a 70kg individual aged 69.8yr with the wild type CYP2C19 and CYP3A4 genotypes.
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- 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 softwareAbametapir The serum concentration of (R)-warfarin can be increased when it is combined with Abametapir. Abatacept The metabolism of (R)-warfarin can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with (R)-warfarin. Abiraterone The serum concentration of (R)-warfarin can be increased when it is combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with (R)-warfarin. Acalabrutinib The serum concentration of (R)-warfarin can be increased when it is combined with Acalabrutinib. Aceclofenac The risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with (R)-warfarin. Acemetacin The risk or severity of bleeding and hemorrhage can be increased when (R)-warfarin is combined with Acemetacin. Acenocoumarol The risk or severity of bleeding can be increased when Acenocoumarol is combined with (R)-warfarin. Acetaminophen The serum concentration of (R)-warfarin can be increased when it is combined with Acetaminophen. 
Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - Food Interactions
- Avoid drastic dietary changes.
- Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.
- Ensure consistent Vitamin K intake.
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum levels of R-warfarin.
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum levels of R-warfarin.
Categories
- Drug Categories
- Anticoagulants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2C18 Substrates
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Vitamin K Antagonists
- 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
- 4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one (CHEBI:87737)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 09CC5J5C8A
- CAS number
- 40281-89-8
- InChI Key
- PJVWKTKQMONHTI-OAHLLOKOSA-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/t15-/m1/s1
- IUPAC Name
- 4-hydroxy-3-[(1R)-3-oxo-1-phenylbutyl]-2H-chromen-2-one
- SMILES
- CC(=O)C[C@H](C1=CC=CC=C1)C1=C(O)C2=C(OC1=O)C=CC=C2
References
- General References
- Lane S, Al-Zubiedi S, Hatch E, Matthews I, Jorgensen AL, Deloukas P, Daly AK, Park BK, Aarons L, Ogungbenro K, Kamali F, Hughes D, Pirmohamed M: The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors. Br J Clin Pharmacol. 2012 Jan;73(1):66-76. doi: 10.1111/j.1365-2125.2011.04051.x. [Article]
- Ragueneau-Majlessi I, Levy RH, Meyerhoff C: Lack of effect of repeated administration of levetiracetam on the pharmacodynamic and pharmacokinetic profiles of warfarin. Epilepsy Res. 2001 Nov;47(1-2):55-63. [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]
- External Links
- PubChem Compound
- 91546
- PubChem Substance
- 99444967
- ChemSpider
- 10533326
- ChEBI
- 87737
- ChEMBL
- CHEMBL251073
- ZINC
- ZINC000084589076
- PDBe Ligand
- RWF
- PDB Entries
- 1h9z / 2bxd
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- 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 32.04 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)
- Not Available
- Spectra
- Not Available
Enzymes
- 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
- Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Very low affinity with little contribution to overall metabolism.
- 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
- Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4. [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
- Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4. [Article]
- Kim SY, Kang JY, Hartman JH, Park SH, Jones DR, Yun CH, Boysen G, Miller GP: Metabolism of R- and S-warfarin by CYP2C19 into four hydroxywarfarins. Drug Metab Lett. 2012 Sep 1;6(3):157-64. [Article]
- 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
- Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4. [Article]
- Kim SY, Kang JY, Hartman JH, Park SH, Jones DR, Yun CH, Boysen G, Miller GP: Metabolism of R- and S-warfarin by CYP2C19 into four hydroxywarfarins. Drug Metab Lett. 2012 Sep 1;6(3):157-64. [Article]
- Lane S, Al-Zubiedi S, Hatch E, Matthews I, Jorgensen AL, Deloukas P, Daly AK, Park BK, Aarons L, Ogungbenro K, Kamali F, Hughes D, Pirmohamed M: The population pharmacokinetics of R- and S-warfarin: effect of genetic and clinical factors. Br J Clin Pharmacol. 2012 Jan;73(1):66-76. doi: 10.1111/j.1365-2125.2011.04051.x. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Vitamin d 24-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
- CYP1A1
- Uniprot ID
- P04798
- Uniprot Name
- Cytochrome P450 1A1
- Molecular Weight
- 58164.815 Da
References
- Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- 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
- Kaminsky LS, Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther. 1997;73(1):67-74. doi: 10.1016/s0163-7258(96)00140-4. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Drug created at September 15, 2010 21:32 / Updated at July 11, 2020 03:42