(R)-warfarin
This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Identification
- Name
- (R)-warfarin
- Accession Number
- DB08496
- Description
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
- Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More- 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
Learn about our commercial Adverse Effects data.
Learn More- Toxicity
- Not Available
- Affected organisms
- 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 Unlock Additional DataAbametapir 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. 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 Acemetacin is combined with (R)-warfarin. Acenocoumarol The metabolism of (R)-warfarin can be decreased when combined with Acenocoumarol. Acetaminophen The metabolism of (R)-warfarin can be increased when combined with Acetaminophen. Acetazolamide The serum concentration of (R)-warfarin can be increased when it is combined with Acetazolamide. Additional Data Available- Extended DescriptionExtended DescriptionAvailable for Purchase
Extended description of the mechanism of action and particular properties of each drug interaction.
Learn more - SeveritySeverityAvailable for Purchase
A severity rating for each drug interaction, from minor to major.
Learn more - Evidence LevelEvidence LevelAvailable for Purchase
A rating for the strength of the evidence supporting each drug interaction.
Learn more - ActionActionAvailable for Purchase
An effect category for each drug interaction. Know how this interaction affects the subject drug.
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)
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. [PubMed:21692828]
- 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. [PubMed:11673021]
- 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. [PubMed:12742309]
- 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. [PubMed:9014207]
- 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. [PubMed:9014207]
- 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. [PubMed:9014207]
- 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. [PubMed:9014207]
- 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. [PubMed:23331088]
- 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. [PubMed:9014207]
- 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. [PubMed:23331088]
- 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. [PubMed:21692828]
- 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. [PubMed:9014207]
- 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. [PubMed:9014207]
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. [PubMed:10592235]
Drug created on September 15, 2010 15:32 / Updated on July 10, 2020 21:42