You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameArgatroban
Accession NumberDB00278  (APRD00105)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Argatroban is a direct, selective thrombin inhibitor. The American College of Cardiologists (ACC) recommend using bivalirudin or argatroban in patients who have had, or at risk for, heparin induced thrombocytopenia (HIT) and are undergoing percutaneous coronary intervention. Argatroban is a non-heparin anticoagulant shown to both normalize platelet count in patients with HIT and prevent the formation of thrombi. Parental anticoagulants must be stopped and a baseline activated partial thromboplastin time must be obtained prior to administering argatroban.

Structure
Thumb
SynonymsNot Available
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Argatrobaninjection1 mg/mLintravenousEagle Pharmaceuticals, Inc.2011-09-06Not applicableUs
Argatrobaninjection, solution100 mg/mLintravenousGlaxo Smith Kline Llc2000-11-28Not applicableUs
Argatrobaninjection1 mg/mLintravenousSandoz Inc2011-09-06Not applicableUs
Argatrobaninjection1 mg/mLintravenousSandoz Inc2011-09-06Not applicableUs
Argatrobansolution125 mg/125mLintravenousSandoz Inc2011-05-09Not applicableUs
Argatrobaninjection, solution1 mg/mLintravenousTeva Parenteral Medicines, Inc.2015-04-27Not applicableUs
Argatrobaninjection250 mg/2.5mLintravenousWest Ward Pharmaceuticals Corp2012-01-05Not applicableUs
Argatrobansolution100 mgintravenousPfizer Canada Inc2002-06-13Not applicableCanada
Argatrobaninjection1 mg/mLintravenousEagle Pharmaceuticals, Inc.2011-09-06Not applicableUs
Argatrobaninjection, solution100 mg/mLintravenousFresenius Kabi USA, LLC2015-03-17Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Argatrobaninjection250 mg/2.5mLintravenousPar Pharmaceutical, Inc.2015-06-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Argatroban monohydrate
141396-28-3
Thumb
  • InChI Key: AIEZTKLTLCMZIA-CZSXTPSTSA-N
  • Monoisotopic Mass: 526.257354142
  • Average Mass: 526.65
DBSALT001826
Categories
UNIIOCY3U280Y3
CAS number74863-84-6
WeightAverage: 508.634
Monoisotopic: 508.246788982
Chemical FormulaC23H36N6O5S
InChI KeyInChIKey=KXNPVXPOPUZYGB-XYVMCAHJSA-N
InChI
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
IUPAC Name
(2R,4R)-1-[(2S)-5-[(diaminomethylidene)amino]-2-[(3R)-3-methyl-1,2,3,4-tetrahydroquinoline-8-sulfonamido]pentanoyl]-4-methylpiperidine-2-carboxylic acid
SMILES
C[C@@H]1CCN([[email protected]](C1)C(O)=O)C(=O)[[email protected]](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[[email protected]](C)C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as peptides. These are compounds containing an amide derived from two or more amino carboxylic acid molecules (the same or different) by formation of a covalent bond from the carbonyl carbon of one to the nitrogen atom of another.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentPeptides
Alternative Parents
Substituents
  • Alpha peptide
  • Alpha-amino acid amide
  • Tetrahydroquinoline
  • Benzenesulfonamide
  • Alpha-amino acid or derivatives
  • Piperidinecarboxylic acid
  • N-acyl-piperidine
  • Aralkylamine
  • Secondary aliphatic/aromatic amine
  • Benzenoid
  • Piperidine
  • Aminosulfonyl compound
  • Tertiary carboxylic acid amide
  • Sulfonyl
  • Sulfonic acid derivative
  • Sulfonamide
  • Tertiary amine
  • Guanidine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Carboximidamide
  • Secondary amine
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Hydrocarbon derivative
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationArgatroban is indicated for prevention and treatment of thrombosis caused by heparin induced thrombocytopenia (HIT). It is also indicated for use in patients with, or at risk for, HIT who are undergoing percutaneous coronary intervention.
PharmacodynamicsArgatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. 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.
Mechanism of actionArgatroban 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.
Related Articles
AbsorptionBioavailability is 100% (intravenous).
Volume of distribution
  • 174 mL/kg
  • 12.18 L [70-kg adult]
Protein binding54%
Metabolism

Liver via hydroxylation and aromatization of the 3-methyltetrahydroquinoline ring. Age and gender do not substantially affect the pharmacodynamic or pharmacokinetic profile of argatroban.

Route of eliminationArgatroban is excreted primarily in the feces (65%), presumably through biliary secretion; 22% is eliminated via urine.
Half life39 and 51 minutes
Clearance
  • 5.1 L/kg/hr [infusion doses up to 40 mcg/kg/min]
ToxicityExcessive bleeding
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Argatroban Action PathwayDrug actionSMP00276
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6195
Blood Brain Barrier-0.8933
Caco-2 permeable-0.7293
P-glycoprotein substrateSubstrate0.8193
P-glycoprotein inhibitor INon-inhibitor0.6701
P-glycoprotein inhibitor IINon-inhibitor0.6802
Renal organic cation transporterNon-inhibitor0.8147
CYP450 2C9 substrateNon-substrate0.5571
CYP450 2D6 substrateNon-substrate0.8861
CYP450 3A4 substrateNon-substrate0.5477
CYP450 1A2 substrateNon-inhibitor0.8849
CYP450 2C9 inhibitorNon-inhibitor0.662
CYP450 2D6 inhibitorNon-inhibitor0.8789
CYP450 2C19 inhibitorNon-inhibitor0.7706
CYP450 3A4 inhibitorNon-inhibitor0.8316
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9636
Ames testNon AMES toxic0.6238
CarcinogenicityNon-carcinogens0.7551
BiodegradationNot ready biodegradable0.9966
Rat acute toxicity1.5767 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9833
hERG inhibition (predictor II)Non-inhibitor0.6071
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
Packagers
Dosage forms
FormRouteStrength
Injectionintravenous1 mg/mL
Injectionintravenous250 mg/2.5mL
Injection, solutionintravenous1 mg/mL
Injection, solutionintravenous100 mg/mL
Solutionintravenous100 mg
Solutionintravenous125 mg/125mL
Prices
Unit descriptionCostUnit
Argatroban 100 mg/ml Solution 2.5ml Vial1546.46USD vial
Argatroban 100 mg/ml vial743.49USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5214052 No1994-06-302014-06-30Us
US7589106 No2007-09-262027-09-26Us
US7687516 No2007-09-262027-09-26Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.221 mg/mLALOGPS
logP0.19ALOGPS
logP-0.97ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)3.07ChemAxon
pKa (Strongest Basic)10.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area180.21 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity133.54 m3·mol-1ChemAxon
Polarizability53.9 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Tomiya Mano, Jin Shiomura, “Argatroban preparations for ophthalmic use.” U.S. Patent US5506241, issued October, 1986.

US5506241
General References
  1. Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. [PubMed:16148288 ]
External Links
ATC CodesB01AE03
AHFS Codes
  • 20:12.04.12
PDB EntriesNot Available
FDA labelDownload (83.7 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AbciximabAbciximab may increase the anticoagulant activities of Argatroban.
AcenocoumarolAcenocoumarol may increase the anticoagulant activities of Argatroban.
Acetylsalicylic acidAcetylsalicylic acid may increase the anticoagulant activities of Argatroban.
AlteplaseAlteplase may increase the anticoagulant activities of Argatroban.
AnistreplaseAnistreplase may increase the anticoagulant activities of Argatroban.
ApixabanApixaban may increase the anticoagulant activities of Argatroban.
ChlorotrianiseneChlorotrianisene may decrease the anticoagulant activities of Argatroban.
Citric AcidCitric Acid may increase the anticoagulant activities of Argatroban.
CollagenaseThe risk or severity of adverse effects can be increased when Argatroban is combined with Collagenase.
Dabigatran etexilateDabigatran etexilate may increase the anticoagulant activities of Argatroban.
DalteparinDalteparin may increase the anticoagulant activities of Argatroban.
DasatinibDasatinib may increase the anticoagulant activities of Argatroban.
DeferasiroxThe risk or severity of adverse effects can be increased when Argatroban is combined with Deferasirox.
Deoxycholic AcidThe risk or severity of adverse effects can be increased when Argatroban is combined with Deoxycholic Acid.
DesogestrelThe therapeutic efficacy of Argatroban can be decreased when used in combination with Desogestrel.
DicoumarolDicoumarol may increase the anticoagulant activities of Argatroban.
DydrogesteroneThe therapeutic efficacy of Argatroban can be decreased when used in combination with Dydrogesterone.
Edetic AcidEdetic Acid may increase the anticoagulant activities of Argatroban.
EdoxabanEdoxaban may increase the anticoagulant activities of Argatroban.
EnoxaparinEnoxaparin may increase the anticoagulant activities of Argatroban.
Ethyl biscoumacetateEthyl biscoumacetate may increase the anticoagulant activities of Argatroban.
Fondaparinux sodiumFondaparinux sodium may increase the anticoagulant activities of Argatroban.
GestodeneThe therapeutic efficacy of Argatroban can be decreased when used in combination with Gestodene.
HeparinHeparin may increase the anticoagulant activities of Argatroban.
HomoharringtonineThe risk or severity of adverse effects can be increased when Argatroban is combined with Homoharringtonine.
Ibritumomab tiuxetanThe risk or severity of adverse effects can be increased when Argatroban is combined with Ibritumomab.
IbrutinibThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Argatroban.
InfliximabInfliximab may increase the anticoagulant activities of Argatroban.
LimaprostThe risk or severity of adverse effects can be increased when Limaprost is combined with Argatroban.
NintedanibThe risk or severity of adverse effects can be increased when Argatroban is combined with Nintedanib.
ObinutuzumabThe risk or severity of adverse effects can be increased when Argatroban is combined with Obinutuzumab.
Omega-3 fatty acidsOmega-3 fatty acids may increase the anticoagulant activities of Argatroban.
Pentosan PolysulfatePentosan Polysulfate may increase the anticoagulant activities of Argatroban.
PhenindionePhenindione may increase the anticoagulant activities of Argatroban.
PhenprocoumonPhenprocoumon may increase the anticoagulant activities of Argatroban.
ProgesteroneThe therapeutic efficacy of Argatroban can be decreased when used in combination with Progesterone.
ReteplaseReteplase may increase the anticoagulant activities of Argatroban.
RidogrelRidogrel may increase the anticoagulant activities of Argatroban.
RivaroxabanArgatroban may increase the anticoagulant activities of Rivaroxaban.
StreptokinaseStreptokinase may increase the anticoagulant activities of Argatroban.
SugammadexSugammadex may increase the anticoagulant activities of Argatroban.
SulodexideSulodexide may increase the anticoagulant activities of Argatroban.
TenecteplaseTenecteplase may increase the anticoagulant activities of Argatroban.
TiboloneTibolone may increase the anticoagulant activities of Argatroban.
TipranavirTipranavir may increase the anticoagulant activities of Argatroban.
TositumomabThe risk or severity of adverse effects can be increased when Argatroban is combined with Tositumomab.
TreprostinilTreprostinil may increase the anticoagulant activities of Argatroban.
UrokinaseUrokinase may increase the anticoagulant activities of Argatroban.
Vitamin EVitamin E may increase the anticoagulant activities of Argatroban.
VorapaxarThe risk or severity of adverse effects can be increased when Vorapaxar is combined with Argatroban.
WarfarinWarfarin may increase the anticoagulant activities of Argatroban.
Food Interactions
  • Herbs and food with anticoagulant/antiplatelet activity. Major interactions may occur with danshen, dong quai, evening primrose oil, gingko, policosanol, willow bark

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Thrombospondin receptor activity
Specific Function:
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
Gene Name:
F2
Uniprot ID:
P00734
Molecular Weight:
70036.295 Da
References
  1. Kawada T, Okada Y, Hoson M, Endo S, Yokoyama M, Kitanaka Y, Kimura K, Abe H, Yamate N: Argatroban, an attractive anticoagulant, for left heart bypass with centrifugal pump for repair of traumatic aortic rupture. Jpn J Thorac Cardiovasc Surg. 1999 Mar;47(3):104-9. [PubMed:10226408 ]
  2. Sakai M, Ohteki H, Narita Y, Naitoh K, Natsuaki M, Itoh T: Argatroban as a potential anticoagulant in cardiopulmonary bypass-studies in a dog model. Cardiovasc Surg. 1999 Mar;7(2):187-94. [PubMed:10353669 ]
  3. Jang IK, Brown DF, Giugliano RP, Anderson HV, Losordo D, Nicolau JC, Dutra OP, Bazzino O, Viamonte VM, Norbady R, Liprandi AS, Massey TJ, Dinsmore R, Schwarz RP Jr: A multicenter, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study. J Am Coll Cardiol. 1999 Jun;33(7):1879-85. [PubMed:10362188 ]
  4. Matsuo T, Kario K, Matsuda S, Yamaguchi N, Kakishita E: Effect of Thrombin Inhibition on Patients with Peripheral Arterial Obstructive Disease: A Multicenter Clinical Trial of Argatroban. J Thromb Thrombolysis. 1995;2(2):131-136. [PubMed:10608016 ]
  5. Serebruany VL, Jang IK, Giugliano RP, Massey TJ, Schwarz Jr RP: A Randomized, Blinded Study of Two Doses of Novastan(R) (Brand of Argatroban) Versus Heparin as Adjunctive Therapy to Recombinant Tissue Plasminogen Activator (Accelerated Administration) in Acute Myocardial Infarction: Rationale and Design of the Myocardial Infarction using Novastan(R) and T-PA (MINT) Study. J Thromb Thrombolysis. 1998;5(1):49-52. [PubMed:10608050 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on June 24, 2016 01:50