Details
Stereochemistry | EPIMERIC |
Molecular Formula | C23H36N6O5S |
Molecular Weight | 508.634 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 4 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
C[C@@H]1CCN([C@H](C1)C(O)=O)C(=O)[C@H](CCCNC(N)=N)NS(=O)(=O)C2=C3NCC(C)CC3=CC=C2
InChI
InChIKey=KXNPVXPOPUZYGB-IOVMHBDKSA-N
InChI=1S/C23H36N6O5S/c1-14-8-10-29(18(12-14)22(31)32)21(30)17(6-4-9-26-23(24)25)28-35(33,34)19-7-3-5-16-11-15(2)13-27-20(16)19/h3,5,7,14-15,17-18,27-28H,4,6,8-13H2,1-2H3,(H,31,32)(H4,24,25,26)/t14-,15?,17+,18-/m1/s1
Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (Ki) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein). Argatroban is capable of inhibiting the action of both free and clot-associated thrombin. Argatroban is indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia.
Argatroban is indicated as an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention (PCI).
Originator
Sources: http://adisinsight.springer.com/drugs/800004018
Curator's Comment: Argatroban was approved and launched during the 1990s in Japan for the initial indications of arterial thrombosis and acute ischaemic stroke.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL204 |
0.04 µM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | ARGATROBAN Approved UseArgatroban is a direct thrombin inhibitor indicated:
• For prophylaxis or treatment of thrombosis in adult patients with
heparin-induced thrombocytopenia (HIT) (1.1)
• As an anticoagulant in adults patients with or at risk for HIT undergoing
percutaneous coronary intervention (PCI) (1.2) Launch Date9.6232322E11 |
|||
Primary | ARGATROBAN Approved UseArgatroban is a direct thrombin inhibitor indicated:
• For prophylaxis or treatment of thrombosis in adult patients with
heparin-induced thrombocytopenia (HIT) (1.1)
• As an anticoagulant in adults patients with or at risk for HIT undergoing
percutaneous coronary intervention (PCI) (1.2) Launch Date9.6232322E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
538.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10730687 |
2.5 μg/kg/min other, intravenous dose: 2.5 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered: |
ARGATROBAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1727.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10730687 |
2.5 μg/kg/min other, intravenous dose: 2.5 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered: |
ARGATROBAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
60.6 min EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10730687 |
2.5 μg/kg/min other, intravenous dose: 2.5 μg/kg/min route of administration: Intravenous experiment type: OTHER co-administered: |
ARGATROBAN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
46% |
ARGATROBAN serum | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
125 mg single, intravenous Overdose Dose: 125 mg Route: intravenous Route: single Dose: 125 mg Sources: |
unhealthy, 74 years n = 1 Health Status: unhealthy Condition: Crohn’s disease, ileorectal fistula Age Group: 74 years Sex: M Population Size: 1 Sources: |
|
125 mg single, intravenous Highest studied dose Dose: 125 mg Route: intravenous Route: single Dose: 125 mg Sources: Page: 6.1 |
unhealthy, adult n = 568 Health Status: unhealthy Condition: thrombosis Age Group: adult Sex: unknown Population Size: 568 Sources: Page: 6.1 |
Other AEs: Haemorrhage... Other AEs: Haemorrhage (57.3%) Sources: Page: 6.1 |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Haemorrhage | 57.3% | 125 mg single, intravenous Highest studied dose Dose: 125 mg Route: intravenous Route: single Dose: 125 mg Sources: Page: 6.1 |
unhealthy, adult n = 568 Health Status: unhealthy Condition: thrombosis Age Group: adult Sex: unknown Population Size: 568 Sources: Page: 6.1 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
yes | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
yes | no (co-administration study) Comment: In 10 healthy subjects, orally administered erythromycin (a potent inhibitor of CYP3A4/5) at 500 mg four times daily for 7 days had no effect on the pharmacokinetics of argatroban at a dose of 1 mcg/kg/min for 5 hours. These data suggest oxidative metabolism by CYP3A4/5 is not an important elimination pathway in-vivo for argatroban. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
yes | no (co-administration study) Comment: In 10 healthy subjects, orally administered erythromycin (a potent inhibitor of CYP3A4/5) at 500 mg four times daily for 7 days had no effect on the pharmacokinetics of argatroban at a dose of 1 mcg/kg/min for 5 hours. These data suggest oxidative metabolism by CYP3A4/5 is not an important elimination pathway in-vivo for argatroban. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/20-883_Acova_biopharmr_P1.pdf#page=34 Page: 34.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Inhibition of collagen-induced platelet aggregation by argatroban in patients with acute cerebral infarction. | 1997 Oct 15 |
|
Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia. | 2002 Sep |
|
Direct thrombin inhibitors for treatment of heparin induced thrombocytopenia, deep vein thrombosis and atrial fibrillation. | 2005 |
|
New antithrombotics in the prevention of thromboembolic disease. | 2005 Aug |
|
Heparin-induced thrombocytopenia in patients administered heparin solely for hemodialysis. | 2006 |
|
When heparin causes thrombosis: significance, recognition, and management of heparin-induced thrombocytopenia in dialysis patients. | 2006 Jul-Aug |
Patents
Sample Use Guides
Initial Dosage: Before administering Argatroban, discontinue heparin therapy and obtain a baseline aPTT. The recommended initial
dose of Argatroban for adult patients without hepatic impairment is 2 mcg/kg/min, administered as a continuous infusion
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25193406
In the presence of 10 nM thrombomodulin (TM) argatroban (1 uM) prolonged clot lysis time and enhanced thrombin generation.
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N0000175980
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N0000175518
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NCI_THESAURUS |
C263
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B01AE03
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1546207
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OCY3U280Y3
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74863-84-6
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SUB05559MIG
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m2039
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6119
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100000091622
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)