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

Details

Stereochemistry EPIMERIC
Molecular Formula C23H36N6O5S
Molecular Weight 508.6361
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ARGATROBAN ANHYDROUS

SMILES

C[C@]1([H])CCN([C@]([H])(C1)C(=O)O)C(=O)[C@]([H])(CCCNC(=N)N)NS(=O)(=O)c2cccc3CC([H])(C)CNc32

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

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

9.6232322E11
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

9.6232322E11
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
Anticoagulation with Novastan (argatroban) in patients with heparin-induced thrombocytopenia and heparin-induced thrombocytopenia and thrombosis syndrome.
1997
Inhibition of collagen-induced platelet aggregation by argatroban in patients with acute cerebral infarction.
1997 Oct 15
The first report of successful carotid stent implant using argatroban anticoagulation in a patient with heparin-induced thrombocytopenia and thrombosis syndrome: a case report.
1998 Jan
Postpartum coronary artery dissection complicated by heparin-induced thrombocytopenia and thrombosis.
2001 Mar
Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia.
2002 Sep
Extremely low doses of lepirudin in a patient with heparin-induced thrombocytopenia, high bleeding risk and renal insufficiency.
2009 Aug
Argatroban dosage requirements and outcomes in intensive care versus non-intensive care patients.
2009 Sep
Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.
2010 Apr
Identification of old drugs as potential inhibitors of HIV-1 integrase - human LEDGF/p75 interaction via molecular docking.
2012 Dec
Therapeutic administration of the direct thrombin inhibitor argatroban reduces hepatic inflammation in mice with established fatty liver disease.
2012 Oct
Use of argatroban and catheter-directed thrombolysis with alteplase in an oncology patient with heparin-induced thrombocytopenia with thrombosis.
2014 May 1
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 ANHYDROUS
Common Name English
ARGATROBAN [INN]
Common Name English
ARGATROBAN [WHO-DD]
Common Name English
ARGATROBAN [MI]
Common Name English
2-PIPERIDINECARBOXYLIC ACID, 1-((2S)-5-((AMINOIMINOMETHYL)AMINO)-1-OXO-2-(((1,2,3,4-TETRAHYDRO-3-METHYL-8-QUINOLINYL)SULFONYL)AMINO)PENTYL)-4-METHYL-, (2R,4R)- ANHYDROUS
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
Systematic Name 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-
Common Name English
Classification Tree Code System Code
NDF-RT N0000175980
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
NDF-RT N0000175518
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
NCI_THESAURUS C263
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
WHO-ATC B01AE03
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C75153
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY
DRUG BANK
DB00278
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY
RXCUI
1546207
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY RxNorm
FDA UNII
OCY3U280Y3
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY
CAS
74863-84-6
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY
EVMPD
SUB05559MIG
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY
PUBCHEM
92722
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY
MERCK INDEX
M2039
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY Merck Index
INN
6119
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY
EPA CompTox
74863-84-6
Created by admin on Sat Jun 26 09:14:41 UTC 2021 , Edited by admin on Sat Jun 26 09:14:41 UTC 2021
PRIMARY