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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

Molecular Formula C23H36N6O5S
Molecular Weight 508.6361
Charge 0
Count
Stereochemistry EPIMERIC
Additional Stereochemistry No
Defined Stereocenters 3 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

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

TargetsConditions

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

962323200000
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

962323200000
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
Health Status: unhealthy
Age Group: 74 years
Sex: M
Sources:
125 mg single, intravenous
Highest studied dose
Dose: 125 mg
Route: intravenous
Route: single
Dose: 125 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
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
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
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
Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia.
2001 Apr 10
Postpartum coronary artery dissection complicated by heparin-induced thrombocytopenia and thrombosis.
2001 Mar
Direct antithrombin agents ameliorate disseminated intravascular coagulation in suspected heparin-induced thrombocytopenia thrombosis syndrome.
2002 Jul
Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia.
2002 Sep
Effects of argatroban and heparin on thrombus formation and tissue plasminogen activator-induced thrombolysis in a microvascular thrombosis model.
2003 Jan 1
Direct thrombin inhibitor therapy in the cardiovascular patient.
2003 Oct 15
Effect of direct thrombin inhibitors, bivalirudin, lepirudin, and argatroban, on prothrombin time and INR values.
2004 Apr
Severe argatroban-induced coagulopathy in a patient with a history of heparin-induced thrombocytopenia.
2004 Dec
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
Heparin-induced thrombocytopenia in patients administered heparin solely for hemodialysis.
2006
Heparin-induced thrombocytopenia: treatment options and special considerations.
2007 Apr
Risk factors for major bleeding in patients with heparin-induced thrombocytopenia treated with argatroban: a retrospective study.
2008 Dec
Bivalirudin.
2008 May
Reducing harm associated with anticoagulation: practical considerations of argatroban therapy in heparin-induced thrombocytopenia.
2009
Extremely low doses of lepirudin in a patient with heparin-induced thrombocytopenia, high bleeding risk and renal insufficiency.
2009 Aug
A report of outcomes after orthotopic liver transplant with allografts from heparin antibody-positive donors.
2009 Mar
Argatroban dosage requirements and outcomes in intensive care versus non-intensive care patients.
2009 Sep
Heparin induced thrombocytopenia and re-thrombosis associated with warfarin and fondaparinux in a child.
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
Route of Administration: Intravenous
In the presence of 10 nM thrombomodulin (TM) argatroban (1 uM) prolonged clot lysis time and enhanced thrombin generation.
Substance Class Chemical
Created
by admin
on Sat Jun 26 09:14:41 UTC 2021
Edited
by admin
on Sat Jun 26 09:14:41 UTC 2021
Record UNII
OCY3U280Y3
Record Status Validated (UNII)
Record Version
  • Download
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
Related Record Type Details
BINDER->LIGAND
Argatroban is 54% bound to human serum proteins, with binding to albumin and a1-acid glycoprotein being 20% and 34% respectively.
BINDING
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
TARGET -> INHIBITOR
Argatroban is capable of inhibiting the action of both free and clot-associated thrombin.
Ki
SALT/SOLVATE -> PARENT
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC STEADY-STATE

Biological Half-life PHARMACOKINETIC