Details
Stereochemistry | RACEMIC |
Molecular Formula | C19H15O4.K |
Molecular Weight | 346.4183 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
[K+].CC(=O)CC(C1=CC=CC=C1)C2=C([O-])C3=CC=CC=C3OC2=O
InChI
InChIKey=WSHYKIAQCMIPTB-UHFFFAOYSA-M
InChI=1S/C19H16O4.K/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;/q;+1/p-1
Molecular Formula | C19H15O4 |
Molecular Weight | 307.32 |
Charge | -1 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
Molecular Formula | K |
Molecular Weight | 39.0983 |
Charge | 1 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Warfarin is an anticoagulant drug normally used to prevent blood clot formation as well as migration. Warfarin is marketed under the brand name Coumadin among others. Coumadin (crystalline warfarin sodium) is an anticoagulant which acts by inhibiting vitamin
K-dependent coagulation factors. Chemically, it is 3-(α-acetonylbenzyl)-4-hydroxycoumarin and is a racemic mixture of the R- and S-enantiomers. Coumadin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. It is also indicated for the prophylaxis and/or treatment of the thromboembolic
complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide. The degree of depression is dependent upon the dosage
administered and, in part, by the patient’s VKORC1 genotype. Therapeutic doses of warfarin decrease the total amount of the active form of each vitamin K dependent clotting factor made by the liver by approximately 30% to 50%.
CNS Activity
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
24.7 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | COUMADIN Approved UseWarfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Launch Date1954 |
|||
Preventing | COUMADIN Approved UseWarfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Launch Date1954 |
|||
Preventing | COUMADIN Approved UseWarfarin sodium tablets are indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. Warfarin sodium tablets are indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin sodium tablets are indicated to reduce the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction. Launch Date1954 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2186 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19552747 |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
WARFARIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
52278 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19552747 |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
WARFARIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
32.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19552747 |
25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered: |
WARFARIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
7 day |
single, oral |
WARFARIN unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1% |
single, oral |
WARFARIN unknown | Homo sapiens population: UNHEALTHY age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
125 mg single, oral Overdose Dose: 125 mg Route: oral Route: single Dose: 125 mg Co-administed with:: oxycodone, p.o(200 mg, single) Sources: Page: p.718 |
unhealthy, 43 n = 1 Health Status: unhealthy Condition: Deep venous thromboses Age Group: 43 Sex: M Population Size: 1 Sources: Page: p.718 |
Disc. AE: Vomiting, Loss of consciousness... AEs leading to discontinuation/dose reduction: Vomiting Sources: Page: p.718Loss of consciousness |
150 mg single, oral Overdose Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: chlorpromazine, p.o(3 g, single) Sources: Page: p.718 |
unhealthy, 44 n = 1 Health Status: unhealthy Condition: Aortic valve replacement Age Group: 44 Sex: M Population Size: 1 Sources: Page: p.718 |
Disc. AE: Drowsiness... AEs leading to discontinuation/dose reduction: Drowsiness Sources: Page: p.718 |
540 mg single, oral Overdose Dose: 540 mg Route: oral Route: single Dose: 540 mg Co-administed with:: clonazepam, p.o(4 mg, single) Sources: Page: p.1 |
healthy, 59 n = 1 Health Status: healthy Age Group: 59 Sex: F Population Size: 1 Sources: Page: p.1 |
|
5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
Disc. AE: Hemoptysis, Hematuria... AEs leading to discontinuation/dose reduction: Hemoptysis Sources: Page: p.1Hematuria Dyspnea Cough |
10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Venous thrombosis|Atrial fibrillation|Myocardial infarction Sources: Page: p.1 |
Disc. AE: Bleeding... AEs leading to discontinuation/dose reduction: Bleeding (grade 5) Sources: Page: p.1 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Loss of consciousness | Disc. AE | 125 mg single, oral Overdose Dose: 125 mg Route: oral Route: single Dose: 125 mg Co-administed with:: oxycodone, p.o(200 mg, single) Sources: Page: p.718 |
unhealthy, 43 n = 1 Health Status: unhealthy Condition: Deep venous thromboses Age Group: 43 Sex: M Population Size: 1 Sources: Page: p.718 |
Vomiting | Disc. AE | 125 mg single, oral Overdose Dose: 125 mg Route: oral Route: single Dose: 125 mg Co-administed with:: oxycodone, p.o(200 mg, single) Sources: Page: p.718 |
unhealthy, 43 n = 1 Health Status: unhealthy Condition: Deep venous thromboses Age Group: 43 Sex: M Population Size: 1 Sources: Page: p.718 |
Drowsiness | Disc. AE | 150 mg single, oral Overdose Dose: 150 mg Route: oral Route: single Dose: 150 mg Co-administed with:: chlorpromazine, p.o(3 g, single) Sources: Page: p.718 |
unhealthy, 44 n = 1 Health Status: unhealthy Condition: Aortic valve replacement Age Group: 44 Sex: M Population Size: 1 Sources: Page: p.718 |
Cough | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
Dyspnea | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
Hematuria | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
Hemoptysis | Disc. AE | 5 mg 1 times / day multiple, oral Recommended Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: Page: p.1 |
unhealthy, 64 n = 1 Health Status: unhealthy Condition: Cardiomyopathy |Atrial fibrillation Age Group: 64 Sex: M Population Size: 1 Sources: Page: p.1 |
Bleeding | grade 5 Disc. AE |
10 mg 1 times / day multiple, oral (max) Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: Page: p.1 |
unhealthy Health Status: unhealthy Condition: Venous thrombosis|Atrial fibrillation|Myocardial infarction Sources: Page: p.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [Ki 8 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | |||
Page: 14.0 |
yes | likely (co-administration study) Comment: Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin Page: 14.0 |
||
Page: 14.0 |
yes | likely (co-administration study) Comment: Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin Page: 14.0 |
||
Page: 14.0 |
yes | yes (pharmacogenomic study) Comment: If the patient’s CYP2C9 and/or VKORC1 genotype are known, consider these ranges in choosing the initial dose. Patients with CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3 may require more prolonged time (>2 to 4 weeks) to achieve maximum INR effect for a given dosage regimen than patients without these CYP variants; Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin; Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin Page: 14.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Prosthetic heart valve thrombosis during dicloxacillin therapy. | 1999 |
|
Potentiation of anticoagulant effect of warfarin caused by enantioselective metabolic inhibition by the uricosuric agent benzbromarone. | 1999 Dec |
|
Anticoagulant induced submucosal hemorrhage mimicking a renal pelvic tumor. | 2000 Jan |
|
Coumarin derivatives and breast-feeding. | 2000 Jun |
|
Thrombolysis and antithrombotic therapy for coronary artery disease. | 2001 Feb |
|
Antithrombotic therapy in valvular heart disease. | 2001 Feb |
|
Oral anticoagulants. Pharmacologic issues for use in the elderly. | 2001 Feb |
|
Thrombus formation on atherosclerotic plaques: pathogenesis and clinical consequences. | 2001 Feb 6 |
|
Cardiac and great vessel thrombosis in Behçet's disease. | 2001 Jan |
|
HIV and thrombosis: a review. | 2001 Jan |
|
Antithrombotic therapy in patients with mechanical and biological prosthetic heart valves. | 2001 Jan |
|
Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. | 2001 Jan |
|
Primary antiphospholipid syndrome masquerading as diabetic retinopathy. | 2001 Jan-Feb |
|
Sneddon's syndrome: a case report. | 2001 Mar |
|
Aspirin does not influence the effect of angiotensin-converting enzyme inhibition on left ventricular ejection fraction 3 months after acute myocardial infarction. | 2001 Mar |
|
Hemoptysis in patients with renal insufficiency : the role of flexible bronchoscopy. | 2001 Mar |
|
Mild head injury, anticoagulants, and risk of intracranial injury. | 2001 Mar 10 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/warfarin.html
Usual Adult Dose for Prevention of Thromboembolism in Atrial Fibrillation Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day
Usual Adult Dose for Myocardial Infarction
Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day
Usual Adult Dose for Deep Vein Thrombosis - Prophylaxis
Initial dose: 2 to 5 mg orally once a day
Maintenance dose: 2 to 10 mg orally once a day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/6712738
Curator's Comment: One strain (TAS) is susceptible and two strains (HW and HS) resistant to the anticoagulant and lethal effects of warfarin.
Vitamin K-reductase activity was inhibited by approximately 13 and 8% respectively when microsomal preparations from TAS and HW animals were incubated with 50 uM vitamin K1 and 10 uM warfarin.
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 16:33:03 GMT 2023
by
admin
on
Fri Dec 15 16:33:03 GMT 2023
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Record UNII |
I47IU4FOCO
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Record Status |
Validated (UNII)
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Record Version |
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EPA PESTICIDE CODE |
86005
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NCI_THESAURUS |
C45597
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2610-86-8
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100000076722
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warfarin-potassium
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C66658
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DTXSID5042324
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32301
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I47IU4FOCO
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SUB15716MIG
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23706212
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82118
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DBSALT001410
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CHEMBL1464
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