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
Thumb
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.
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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
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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.
DrugInteraction
AbametapirThe serum concentration of (R)-warfarin can be increased when it is combined with Abametapir.
AbataceptThe metabolism of (R)-warfarin can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with (R)-warfarin.
AbirateroneThe serum concentration of (R)-warfarin can be increased when it is combined with Abiraterone.
AcalabrutinibThe serum concentration of (R)-warfarin can be increased when it is combined with Acalabrutinib.
AceclofenacThe risk or severity of bleeding and hemorrhage can be increased when Aceclofenac is combined with (R)-warfarin.
AcemetacinThe risk or severity of bleeding and hemorrhage can be increased when Acemetacin is combined with (R)-warfarin.
AcenocoumarolThe metabolism of (R)-warfarin can be decreased when combined with Acenocoumarol.
AcetaminophenThe metabolism of (R)-warfarin can be increased when combined with Acetaminophen.
AcetazolamideThe serum concentration of (R)-warfarin can be increased when it is combined with Acetazolamide.
Additional Data Available
  • Extended Description
    Extended Description
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    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
    Available for Purchase

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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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
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
  1. 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]
  2. 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]
  3. 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]
PubChem Compound
91546
PubChem Substance
99444967
ChemSpider
10533326
ChEBI
87737
ChEMBL
CHEMBL251073
ZINC
ZINC000084589076
PDBe Ligand
RWF
PDB Entries
1h9z / 2bxd

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

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
PropertyValueSource
Water Solubility0.0472 mg/mLALOGPS
logP2.41ALOGPS
logP2.74ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)5.56ChemAxon
pKa (Strongest Basic)-6.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity86.86 m3·mol-1ChemAxon
Polarizability32.04 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9109
Blood Brain Barrier+0.9124
Caco-2 permeable+0.8867
P-glycoprotein substrateSubstrate0.5502
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8863
CYP450 2C9 substrateNon-substrate0.678
CYP450 2D6 substrateSubstrate0.5658
CYP450 3A4 substrateNon-substrate0.6007
CYP450 1A2 substrateNon-inhibitor0.714
CYP450 2C9 inhibitorInhibitor0.7657
CYP450 2D6 inhibitorNon-inhibitor0.9286
CYP450 2C19 inhibitorNon-inhibitor0.9161
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8785
Ames testNon AMES toxic0.6844
CarcinogenicityNon-carcinogens0.9352
BiodegradationNot ready biodegradable0.7474
Rat acute toxicity4.1700 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8768
hERG inhibition (predictor II)Non-inhibitor0.9615
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

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
  1. 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
  1. 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
  1. 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
  1. 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]
  2. 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
  1. 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]
  2. 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]
  3. 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
  1. 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
  1. 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
  1. 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