U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry EPIMERIC
Molecular Formula C23H36N6O5S.H2O
Molecular Weight 526.649
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ARGATROBAN

SMILES

O.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=AIEZTKLTLCMZIA-CZSXTPSTSA-N
InChI=1S/C23H36N6O5S.H2O/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);1H2/t14-,15?,17+,18-;/m1./s1

HIDE SMILES / InChI
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).

CNS Activity

Curator's Comment: Argatroban is capable of passing through the blood brain barrier in rats.

Originator

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

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ARGATROBAN

Approved Use

Argatroban 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 Date

2000
Primary
ARGATROBAN

Approved Use

Argatroban 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 Date

2000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
538.6 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
1727.7 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
60.6 min
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

Funbound

ValueDoseCo-administeredAnalytePopulation
46%
ARGATROBAN serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse 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...
AEs

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
yes
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.
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.
Page: 34.0
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Inhibition of collagen-induced platelet aggregation by argatroban in patients with acute cerebral infarction.
1997 Oct 15
Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.
2001 Apr 10
Heparin-induced thrombocytopenia and thrombosis in a patient with polycythemia vera.
2004 Jul
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 from venous thromboembolism treatment.
2005 Dec
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.
2012 Dec
Patents

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 the presence of 10 nM thrombomodulin (TM) argatroban (1 uM) prolonged clot lysis time and enhanced thrombin generation.
Name Type Language
ARGATROBAN
ORANGE BOOK   USAN   USP-RS   VANDF  
USAN  
Official Name English
ARGATROBAN MONOHYDRATE [MI]
Common Name English
(2R,4R)-4-METHYL-1-(N (SUP 2)-((1,2,3,4-TETRAHYDRO-3-METHYL-8-QUINOLYL)SULFONYL)-L-ARGINYL)PIPECOLIC ACID, MONOHYDRATE
Common Name English
GN-1600
Code English
Argatroban monohydrate [WHO-DD]
Common Name English
ARGATROBAN MONOHYDRATE
MI   WHO-DD  
Common Name English
ARGIPIDINE
Common Name English
ARGATROBAN [USAN]
Common Name English
GN1600
Code English
2-PIPERIDINECARBOXYLIC ACID, 1-(5-((AMINOIMINOMETHYL)AMINO)-1-OXO-2-(((1,2,3,4-TETRAHYDRO-3-METHYL-8-QUINOLINYL)SULFONYL)AMINO)PENTYL)-4-METHYL-, MONOHYDRATE
Common Name English
NOVASTAN
Brand Name English
MCI-9038
Code English
ARGATROBAN HYDRATE [JAN]
Common Name English
ARGATROBAN HYDRATE
JAN  
Common Name English
ARGATROBAN [USP MONOGRAPH]
Common Name English
MD-805
Code English
ARGATROBAN [ORANGE BOOK]
Common Name English
DK-7419
Code English
ARGATROBAN [VANDF]
Common Name English
ARGATROBAN [USP-RS]
Common Name English
Classification Tree Code System Code
NDF-RT N0000175980
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
NCI_THESAURUS C263
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
NDF-RT N0000009963
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
NDF-RT N0000175518
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
WHO-VATC QB01AE03
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
WHO-ATC B01AE03
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LOINC 68981-0
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
Code System Code Type Description
EPA CompTox
DTXSID5057888
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
LACTMED
Argatroban
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
USAN
II-67
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
IUPHAR
6385
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
CAS
141396-28-3
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PRIMARY
DAILYMED
IY90U61Z3S
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PRIMARY
EVMPD
SUB48842
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PRIMARY
SMS_ID
100000132863
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PRIMARY
WIKIPEDIA
ARGATROBAN
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
FDA UNII
IY90U61Z3S
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
MESH
C031942
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
NCI_THESAURUS
C28833
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
DRUG BANK
DB00278
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
RXCUI
15202
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PRIMARY RxNorm
PUBCHEM
92721
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PRIMARY
RS_ITEM_NUM
1042408
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PRIMARY
ChEMBL
CHEMBL1166
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PRIMARY
EVMPD
SUB05559MIG
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY
MERCK INDEX
m2039
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY Merck Index
DRUG CENTRAL
239
Created by admin on Sat Dec 16 08:25:09 GMT 2023 , Edited by admin on Sat Dec 16 08:25:09 GMT 2023
PRIMARY