Identification

Name
Dabigatran etexilate
Accession Number
DB06695
Type
Small Molecule
Groups
Approved
Description

Dabigatran etexilate is an oral prodrug that is metabolized by a serum esterase to dabigatran. It is a synthetic, competitive and reversible direct thrombin inhibitor. Inhibition of thrombin disrupts the coagulation cascade and inhibits the formation of clots. Dabigatran etexilate may be used to decrease the risk of venous thromboembolic events in patients who have undergone total hip or knee replacement surgery, or to prevent stroke and systemic embolism in patients with atrial fibrillation, in whom anticoagulation therapy is indicated. In contrast to warfarin, because its anticoagulant effects are predictable, lab monitoring is not necessary. FDA approved on October 19, 2010.

Structure
Thumb
Synonyms
  • Ethyl 3-[[[4-[[[(hexyloxyl)carbonyl]amino]iminomethyl]phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl](pyridin-2-yl)amino] propanoate
External IDs
BIBR 1048 / BIBR 1048 BS RS1 / BIBR-1048 / BIBR-1048-BS-RS1
Product Ingredients
IngredientUNIICASInChI Key
Dabigatran etexilate mesilateSC7NUW5IIT872728-81-9XETBXHPXHHOLOE-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PradaxaCapsule75 mgOralBoehringer Ingelheim2008-03-18Not applicableEu
PradaxaCapsule75 mg/1OralBoehringer Ingelheim Pharmaceuticals Inc.2010-11-082010-10-25Us
PradaxaCapsule110 mgOralBoehringer Ingelheim2008-03-18Not applicableEu
PradaxaCapsule75 mgOralBoehringer Ingelheim (Canada) Ltd Ltee2008-07-03Not applicableCanada
PradaxaCapsule150 mg/1OralBoehringer Ingelheim2010-10-26Not applicableUs
PradaxaCapsule150 mgOralBoehringer Ingelheim2008-03-18Not applicableEu
PradaxaCapsule75 mg/1OralBoehringer Ingelheim2011-08-08Not applicableUs
PradaxaCapsule150 mgOralBoehringer Ingelheim2008-03-18Not applicableEu
PradaxaCapsule110 mgOralBoehringer Ingelheim2008-03-18Not applicableEu
PradaxaCapsule150 mgOralBoehringer Ingelheim2008-03-18Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-dabigatranCapsule110 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-dabigatranCapsule75 mgOralApotex CorporationNot applicableNot applicableCanada
Apo-dabigatranCapsule150 mgOralApotex CorporationNot applicableNot applicableCanada
Teva-dabigatranCapsule75 mgOralTevaNot applicableNot applicableCanada
Teva-dabigatranCapsule150 mgOralTevaNot applicableNot applicableCanada
International/Other Brands
Pradax (Boehringer Ingelheim) / Rendix
Categories
UNII
2E18WX195X
CAS number
211915-06-9
Weight
Average: 627.7332
Monoisotopic: 627.316917457
Chemical Formula
C34H41N7O5
InChI Key
KSGXQBZTULBEEQ-UHFFFAOYSA-N
InChI
InChI=1S/C34H41N7O5/c1-4-6-7-10-21-46-34(44)39-32(35)24-12-15-26(16-13-24)37-23-30-38-27-22-25(14-17-28(27)40(30)3)33(43)41(20-18-31(42)45-5-2)29-11-8-9-19-36-29/h8-9,11-17,19,22,37H,4-7,10,18,20-21,23H2,1-3H3,(H2,35,39,44)
IUPAC Name
ethyl 3-(1-{2-[({4-[amino({[(hexyloxy)carbonyl]imino})methyl]phenyl}amino)methyl]-1-methyl-1H-1,3-benzodiazol-5-yl}-N-(pyridin-2-yl)formamido)propanoate
SMILES
CCCCCCOC(=O)N=C(N)C1=CC=C(NCC2=NC3=C(C=CC(=C3)C(=O)N(CCC(=O)OCC)C3=CC=CC=N3)N2C)C=C1

Pharmacology

Indication

Dabigatran is indicated for the prevention of venous thromboembolic events in patients who have undergone elective hip or knee replacement surgery (based on RE-NOVATE, RE-MODEL, and RE-MOBILIZE trials). In 2010, it was approved in the US and Canada for prevention of stroke and systemic embolism in patients with atrial fibrillation (approval based on the RE-LY trial). Contraindications: severe renal impairment (CrCL < 30 ml/min); haemorrhagic manifestations, bleeding diathesis or spontaneous or pharmacologic impairment of haemostasis; lesions at risk of clinically significant bleeding (e.g. extensive cerebral infarction (haemorrhagic or ischemic) in the last 6 months, active peptic ulcer disease); concomitant treatment with P-glycoprotein inhibitors (e.g. oral ketoconazole, verapamil); and those with known hypersensitivity to dabigatran, dabigatran etexilate or any ingredient used in the formulation or component of the container. As of December 2012, dabigatran is contraindicated in patients with mechanical prosthetic heart valves.

Associated Conditions
Pharmacodynamics

Dabigatran directly inhibits thrombin in a concentration-dependent, reversible, specific, and competitive manner which results in a prolongation of aPTT (partial thromboplastin time), ECT (Ecarin clotting time), and TT (thrombin time). It may increase INR but this laboratory parameter is relatively insensitive to the activity of dabigatran.

Mechanism of action

Dabigatran etexilate is an inactive pro-drug that is converted to dabigatran, the active form, by esterase-catalyzed hydrolysis in the plasma and liver. Dabigatran, the main active principle in plasma, is a rapid-acting competitive and reversible direct inhibitor of thrombin. Thrombin, a serine protease, is responsible for the conversion of fibrinogen to fibrin in the coagulation cascade. Inhibition of thrombin consequently prevents thrombus development. Dabigatran inhibits free thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregation.

TargetActionsOrganism
AProthrombin
inhibitor
Human
Absorption

Peak plasma concentrations were achieved in 6 hours in post surgical patients. In healthy patients, maximum concentrations were achieved in 0.5 to 2 hours. The absolute bioavailability of dabigatran in the body after administration of dabigatran etexilate was 6.5%. Food does not affect the bioavailability of dabigatran etexilate, but it delays the time to peak plasma concentrations by 2 hours. Oral bioavailability may increase by up to 75% when pellets are taken out of the hydroxypropylmethylcellulose (HPMC) capsule. Therefore, capsules should not be opened and pellets taken alone. Furthermore, although absorption of dabigatran etexilate is independent of gastrointestinal acidity, coadministration of pantoprazole (proton pump inhibitor) may reduce the bioavailability of dabigatran. Despite this finding, dose adjustment is not required.

Volume of distribution

Moderate tissue distribution with a Vd of 60-70L. Accumulation factor, twice daily dosing = 2

Protein binding

Relatively low binding (34-35%) to plasma proteins.

Metabolism

CYP450 enzymes are not involved in the metabolism of dabigatran thus is not expected to interact with drugs metabolized by CYP isoenzymes. Dabigatran is typically metabolised by esterases and microsomal carboxylesterases. Pharmacologically active acylglucoronides are formed via conjugation. Four positional isomers, 1-O, 2-O, 3-O, and 4-O, acylglucuronides exist, each accounting for less than 10% of total plasma dabagatran.

Route of elimination

Mainly excreted in urine (85%). Fecal excretion accounts for 6% of the orally administered dose. Dabigatran is primarily eliminated unchanged via the kidneys at a rate of 100 ml/min corresponding to the glomerular filtration rate.

Half life

12-14 hours in healthy volunteers. 14-17 hours in patients treated for prevention of venous thromboembolism following hip- or knee-replacement surgery.

Clearance
Not Available
Toxicity

The most common adverse reactions include dyspepsia or gastritis-like symptoms. The approximate lethal dose (LD50) in rats and mice was observed at single oral doses of > 2000 mg/kg. Oral doses of 600 mg/kg did not induce any toxicologically meaningful changes in dogs and Rhesus monkeys. Dabigatran was well-tolerated in rats and Rhesus monkeys during repeat-dose toxicity studies. No evidence of mutagenic potential.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe therapeutic efficacy of Dabigatran etexilate can be increased when used in combination with (1,2,6,7-3H)Testosterone.
(R)-warfarinDabigatran etexilate may increase the anticoagulant activities of (R)-warfarin.
(S)-WarfarinDabigatran etexilate may increase the anticoagulant activities of (S)-Warfarin.
1-TestosteroneThe therapeutic efficacy of Dabigatran etexilate can be increased when used in combination with 1-Testosterone.
18-methyl-19-nortestosteroneThe therapeutic efficacy of Dabigatran etexilate can be increased when used in combination with 18-methyl-19-nortestosterone.
4-hydroxycoumarinDabigatran etexilate may increase the anticoagulant activities of 4-hydroxycoumarin.
4-HydroxytestosteroneThe therapeutic efficacy of Dabigatran etexilate can be increased when used in combination with 4-Hydroxytestosterone.
5beta-dihydrotestosteroneThe therapeutic efficacy of Dabigatran etexilate can be increased when used in combination with 5beta-dihydrotestosterone.
AbacavirAbacavir may decrease the excretion rate of Dabigatran etexilate which could result in a higher serum level.
AbciximabDabigatran etexilate may increase the anticoagulant activities of Abciximab.
Food Interactions
  • St. John's Wort

References

Synthesis Reference

Christian Filser, Wolfgang Dersch, Rainer Hamm, Arndt Hausherr, Gunter Koch, Ulrich Scholz, Georg Zerban, "METHOD FOR PRODUCING AN INTERMEDIATE PRODUCT OF DABIGATRAN ETEXILATE." U.S. Patent US20110118471, issued May 19, 2011.

US20110118471
General References
  1. Bauer KA: New oral anticoagulants in development: potential for improved safety profiles. Rev Neurol Dis. 2010;7(1):1-8. [PubMed:20410856]
  2. Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, Pogue J, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R, Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L: Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009 Sep 17;361(12):1139-51. doi: 10.1056/NEJMoa0905561. Epub 2009 Aug 30. [PubMed:19717844]
  3. Wolowacz SE, Roskell NS, Plumb JM, Caprini JA, Eriksson BI: Efficacy and safety of dabigatran etexilate for the prevention of venous thromboembolism following total hip or knee arthroplasty. A meta-analysis. Thromb Haemost. 2009 Jan;101(1):77-85. [PubMed:19132192]
  4. Ginsberg JS, Davidson BL, Comp PC, Francis CW, Friedman RJ, Huo MH, Lieberman JR, Muntz JE, Raskob GE, Clements ML, Hantel S, Schnee JM, Caprini JA: Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty. 2009 Jan;24(1):1-9. doi: 10.1016/j.arth.2008.01.132. Epub 2008 Apr 14. [PubMed:18534438]
  5. Eriksson BI, Dahl OE, Buller HR, Hettiarachchi R, Rosencher N, Bravo ML, Ahnfelt L, Piovella F, Stangier J, Kalebo P, Reilly P: A new oral direct thrombin inhibitor, dabigatran etexilate, compared with enoxaparin for prevention of thromboembolic events following total hip or knee replacement: the BISTRO II randomized trial. J Thromb Haemost. 2005 Jan;3(1):103-11. [PubMed:15634273]
  6. Di Nisio M, Middeldorp S, Buller HR: Direct thrombin inhibitors. N Engl J Med. 2005 Sep 8;353(10):1028-40. [PubMed:16148288]
  7. Stangier J, Eriksson BI, Dahl OE, Ahnfelt L, Nehmiz G, Stahle H, Rathgen K, Svard R: Pharmacokinetic profile of the oral direct thrombin inhibitor dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement. J Clin Pharmacol. 2005 May;45(5):555-63. [PubMed:15831779]
  8. Ezekowitz MD, Reilly PA, Nehmiz G, Simmers TA, Nagarakanti R, Parcham-Azad K, Pedersen KE, Lionetti DA, Stangier J, Wallentin L: Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study). Am J Cardiol. 2007 Nov 1;100(9):1419-26. Epub 2007 Aug 17. [PubMed:17950801]
  9. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Kalebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, Buller HR: Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost. 2007 Nov;5(11):2178-85. [PubMed:17764540]
  10. Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Prins MH, Hettiarachchi R, Hantel S, Schnee J, Buller HR: Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet. 2007 Sep 15;370(9591):949-56. [PubMed:17869635]
  11. Scaglione F: New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013 Feb;52(2):69-82. doi: 10.1007/s40262-012-0030-9. [PubMed:23292752]
External Links
Human Metabolome Database
HMDB0015641
KEGG Drug
D07144
PubChem Compound
6445226
PubChem Substance
99443249
ChemSpider
4948999
BindingDB
50432209
ChEBI
70746
ChEMBL
CHEMBL539697
PharmGKB
PA165958369
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Dabigatran
ATC Codes
B01AE07 — Dabigatran etexilate
AHFS Codes
  • 20:12.04.12 — Direct Thrombin Inhibitors
FDA label
Download (431 KB)
MSDS
Download (99.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentHealthy Volunteers1
1CompletedNot AvailableCardiovascular Disease (CVD) / Chronic Renal Failure (CRF)1
1CompletedNot AvailableHealthy Volunteers2
1CompletedBasic ScienceDisorders, Blood Coagulation1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedOtherHealthy Volunteers2
1CompletedOtherProstatic Neoplasms1
1CompletedTreatmentHealthy Volunteers29
1CompletedTreatmentHepatic Insufficiency1
1CompletedTreatmentImpaired Renal Function1
1CompletedTreatmentInterstitial Lung Disease (ILD) / Scleroderma1
1CompletedTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD)1
1CompletedTreatmentRenal Insufficiency,Chronic1
1CompletedTreatmentThrombotic events1
1TerminatedTreatmentHealthy Volunteers1
2Active Not RecruitingTreatmentMinor Ischemic Stroke / Transient Ischaemic Attack (TIA)1
2CompletedNot AvailableVenous Thromboembolism (VTE)2
2CompletedPreventionArthroplasty, Replacement, Knee / Thrombosis, Venous1
2CompletedPreventionNonvalvular Atrial Fibrillation1
2CompletedPreventionVenous Thromboembolism (VTE)1
2CompletedTreatmentCoronary Heart Disease (CHD)1
2CompletedTreatmentHeart Catheterization1
2CompletedTreatmentMinor Ischemic Stroke / Transient Ischaemic Attack (TIA)1
2CompletedTreatmentVenous Thromboembolism (VTE)3
2TerminatedPreventionHeart Valve Diseases1
2TerminatedPreventionHeart Valve Prosthesis / Thromboembolism1
2TerminatedPreventionNonvalvular Atrial Fibrillation / Strokes1
2TerminatedTreatmentHaemorrhage / Thrombotic events1
2Unknown StatusTreatmentCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy1
2WithdrawnTreatmentVenous Thromboembolism (VTE)1
2, 3TerminatedTreatmentPrimary Disease1
3Active Not RecruitingTreatmentMyocardial Injury After Noncardiac Surgery (MINS)1
3CompletedPreventionArthroplasty, Replacement, Hip / Thromboembolism1
3CompletedPreventionArthroplasty, Replacement, Knee / Thromboembolism2
3CompletedPreventionSecondary Preventions / Strokes1
3CompletedPreventionVenous Thromboembolism (VTE)2
3CompletedTreatmentHematoma1
3CompletedTreatmentNonvalvular Atrial Fibrillation / Percutaneous Coronary Intervention1
3CompletedTreatmentThromboembolism4
3Not Yet RecruitingPreventionNonvalvular Atrial Fibrillation / Thromboembolism1
3Not Yet RecruitingTreatmentNonvalvular Atrial Fibrillation1
3RecruitingPreventionAtrial Flutter / Intracranial Hemorrhage, Hypertensive / Intracranial Hemorrhages / Intraventricular Hemorrhage / Microhaemorrhage / Nonvalvular Atrial Fibrillation / Small Vessel Cerebrovascular Disease / Subarachnoid Hemorrhage / Subdural haematoma1
3RecruitingPreventionSecondary Preventions / Venous Thromboembolism (VTE)1
3RecruitingTreatmentCerebral Venous Thrombosis1
3RecruitingTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
3RecruitingTreatmentVenous Thromboembolism (VTE)1
4Active Not RecruitingSupportive CareAtrial Flutter / Nonvalvular Atrial Fibrillation1
4CompletedBasic ScienceVenous Thromboembolism (VTE)1
4CompletedPreventionArthroplasty, Replacement / Moderate Renal Impairment (CrCl 30-50 mL/Min) / Prevention of Venous Thromboembolism1
4CompletedPreventionNonvalvular Atrial Fibrillation2
4CompletedTreatmentCoronary Heart Disease (CHD)1
4CompletedTreatmentNonvalvular Atrial Fibrillation4
4Enrolling by InvitationPreventionDevice Related Thrombus / Left Atrial Appendage Thrombosis / Nonvalvular Atrial Fibrillation / Watchman LAA Closure Device1
4Enrolling by InvitationTreatmentNonvalvular Atrial Fibrillation1
4Not Yet RecruitingTreatmentCoronary Artery Disease / Nonvalvular Atrial Fibrillation1
4RecruitingOtherCerebral Ischemic Events / Cognition Disorders / Dementias1
4RecruitingPreventionNonvalvular Atrial Fibrillation3
4RecruitingTreatment(Atrial Fibrillation) or (Atrial Flutter) / Thrombosis of Left Atrial Appendage1
4RecruitingTreatmentAngiographically Confirmed Acute Massive Pulmonary Embolism Treated With Endovascular Mechanical Fragmentation and Thrombolytic Therapy / Dabigatran Etexilate / Pulmonary Embolism (PE) / Recurrence of DVT / Warfarin1
4RecruitingTreatmentCardioembolic Events / Nonvalvular Atrial Fibrillation / Oral Anticoagulation1
4RecruitingTreatmentDeep Vein Thrombosis (DVT) / Pulmonary Embolism (PE)1
4RecruitingTreatmentDiabetes Mellitus (DM)1
4RecruitingTreatmentLeft Atrial Thrombosis / Nonvalvular Atrial Fibrillation1
4RecruitingTreatmentNonvalvular Atrial Fibrillation2
4RecruitingTreatmentNonvalvular Atrial Fibrillation / Valve Heart Disease1
4RecruitingTreatmentPulmonary Embolism (PE)1
4TerminatedDiagnosticNonvalvular Atrial Fibrillation1
4TerminatedTreatmentAcute Coronary Syndromes (ACS) / Atherosclerosis / Coronary Heart Disease (CHD) / Nonvalvular Atrial Fibrillation1
4Unknown StatusNot AvailableAnticoagulant Overdosage / Anticoagulant-induced Bleeding / Hemorrhage / Thrombotic events1
4WithdrawnTreatmentCoronary Heart Disease (CHD) / Non ST Segment Elevation Myocardial Infarction (NSTEMI) / ST Elevation Myocardial Infarction (STEMI) / Stable Angina (SA) / Unstable Angina (UA)1
4WithdrawnTreatmentThromboembolism1
Not AvailableActive Not RecruitingNot AvailableAnticoagulation1
Not AvailableActive Not RecruitingNot AvailableMajor Bleeding / Myocardial Infarction / Nonvalvular Atrial Fibrillation / Stroke, Ischemic / Systemic Embolization / The Mortality Rate1
Not AvailableActive Not RecruitingNot AvailableNonvalvular Atrial Fibrillation3
Not AvailableCompletedNot AvailableAnticoagulants / Nonvalvular Atrial Fibrillation / Pharmacoepidemiology1
Not AvailableCompletedNot AvailableHemorrhage / Nonvalvular Atrial Fibrillation1
Not AvailableCompletedNot AvailableMajor Bleeding / Myocardial Infarction / Nonvalvular Atrial Fibrillation / Stroke, Ischemic / Systemic Embolization / The Mortality Rate1
Not AvailableCompletedNot AvailableMajor Bleeding / Venous Thromboembolism (VTE)1
Not AvailableCompletedNot AvailableNonvalvular Atrial Fibrillation13
Not AvailableCompletedNot AvailableNonvalvular Atrial Fibrillation / Strokes Thrombotic1
Not AvailableCompletedNot AvailableStrokes1
Not AvailableCompletedNot AvailableStrokes / Transient Ischaemic Attack (TIA)1
Not AvailableCompletedNot AvailableUnsuspected Pulmonary Embolism1
Not AvailableCompletedTreatmentCoronary Artery Disease1
Not AvailableCompletedTreatmentNonvalvular Atrial Fibrillation1
Not AvailableEnrolling by InvitationTreatmentAcute DVT of Lower Extremity1
Not AvailableNot Yet RecruitingNot AvailableNon-valvular Atrial Fibrillation (NVAF)1
Not AvailableNot Yet RecruitingNot AvailableNonvalvular Atrial Fibrillation1
Not AvailableNot Yet RecruitingBasic ScienceIdiopathic Pulmonary Fibrosis (IPF) / Interstitial Lung Disease (ILD) / IPF1
Not AvailableRecruitingNot AvailableCardioembolic Stroke1
Not AvailableRecruitingHealth Services ResearchNeoplasms / Thrombosis, Venous1
Not AvailableRecruitingPreventionNonvalvular Atrial Fibrillation / Strokes1
Not AvailableRecruitingSupportive CareHemorrhage / Nonvalvular Atrial Fibrillation / Periodontal Diseases1
Not AvailableRecruitingTreatmentAnticoagulant Adverse Reaction / Hemorrhage / Nonvalvular Atrial Fibrillation / Thrombotic events1
Not AvailableRecruitingTreatmentBlood Clots / Deep Vein Thrombosis (DVT) / Malignancies / Pulmonary Embolism (PE) / Venous Thromboembolism (VTE)1
Not AvailableTerminatedNot AvailableArthroplasty, Replacement / Venous Thromboembolism (VTE)1
Not AvailableUnknown StatusSupportive CareBlood Loss / Osteoarthritis, Hip1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral110 mg/1
CapsuleOral110 mg
CapsuleOral150 mg/1
CapsuleOral150 mg
CapsuleOral75 mg
CapsuleOral75 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9034822No2011-01-202031-01-20Us
US6087380No1998-02-182018-02-18Us
US7932273No2005-09-072025-09-07Us
US7866474No2007-08-312027-08-31Us
US9925174No2003-06-142023-06-14Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)180 +/- 3 (DSC: 10 K min^-1 heating rate)Not Available
water solubility1.8mg/ml, partly soluble MSDS
logP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00466 mg/mLALOGPS
logP5.17ALOGPS
logP4.59ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)17.89ChemAxon
pKa (Strongest Basic)3.87ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area154.03 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity176.43 m3·mol-1ChemAxon
Polarizability71.11 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.942
Blood Brain Barrier+0.8673
Caco-2 permeable-0.7014
P-glycoprotein substrateSubstrate0.7412
P-glycoprotein inhibitor IInhibitor0.7539
P-glycoprotein inhibitor IIInhibitor0.8443
Renal organic cation transporterNon-inhibitor0.701
CYP450 2C9 substrateNon-substrate0.858
CYP450 2D6 substrateNon-substrate0.837
CYP450 3A4 substrateSubstrate0.6154
CYP450 1A2 substrateNon-inhibitor0.6906
CYP450 2C9 inhibitorNon-inhibitor0.5102
CYP450 2D6 inhibitorNon-inhibitor0.8417
CYP450 2C19 inhibitorInhibitor0.5157
CYP450 3A4 inhibitorInhibitor0.781
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5789
Ames testNon AMES toxic0.6292
CarcinogenicityNon-carcinogens0.8065
BiodegradationNot ready biodegradable0.9931
Rat acute toxicity2.7093 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9047
hERG inhibition (predictor II)Inhibitor0.6181
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00kk-0981100000-78856b63936cf67ebce2
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004r-0292116000-55b368cbe92da888e681

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzimidazoles
Sub Class
Not Available
Direct Parent
Benzimidazoles
Alternative Parents
Phenylalkylamines / Aniline and substituted anilines / Secondary alkylarylamines / Pyridines and derivatives / N-substituted imidazoles / Imidolactams / Tertiary carboxylic acid amides / Heteroaromatic compounds / Amino acids and derivatives / Carboxylic acid esters
show 10 more
Substituents
Benzimidazole / Aniline or substituted anilines / Phenylalkylamine / Secondary aliphatic/aromatic amine / Aralkylamine / Monocyclic benzene moiety / N-substituted imidazole / Pyridine / Benzenoid / Imidolactam
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
carboxylic ester, carboxamidine, beta-alanine derivative, pyridines, aromatic amide, benzimidazoles (CHEBI:70746)

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 homeostas...
Gene Name
F2
Uniprot ID
P00734
Uniprot Name
Prothrombin
Molecular Weight
70036.295 Da
References
  1. Squizzato A, Dentali F, Steidl L, Ageno W: New direct thrombin inhibitors. Intern Emerg Med. 2009 Dec;4(6):479-84. doi: 10.1007/s11739-009-0314-8. Epub 2009 Sep 15. [PubMed:19756950]
  2. Liesenfeld KH, Schafer HG, Troconiz IF, Tillmann C, Eriksson BI, Stangier J: Effects of the direct thrombin inhibitor dabigatran on ex vivo coagulation time in orthopaedic surgery patients: a population model analysis. Br J Clin Pharmacol. 2006 Nov;62(5):527-37. [PubMed:17061960]
  3. Karthikeyan G, Eikelboom JW, Hirsh J: Dabigatran: ready for prime time? Pol Arch Med Wewn. 2010 Apr;120(4):137-42. [PubMed:20424539]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Triglyceride lipase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Hydrolyzes aromatic and aliphatic esters, but has no catalytic activity toward amides or a fatty acy...
Gene Name
CES1
Uniprot ID
P23141
Uniprot Name
Liver carboxylesterase 1
Molecular Weight
62520.62 Da
References
  1. Hu ZY, Parker RB, Herring VL, Laizure SC: Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism. Anal Bioanal Chem. 2013 Feb;405(5):1695-704. doi: 10.1007/s00216-012-6576-4. Epub 2012 Dec 14. [PubMed:23239178]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Methylumbelliferyl-acetate deacetylase activity
Specific Function
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs. Shows high catalytic efficiency for hydrolysis of cocaine, 4-methylumbelliferyl acetate, heroin and ...
Gene Name
CES2
Uniprot ID
O00748
Uniprot Name
Cocaine esterase
Molecular Weight
61806.41 Da
References
  1. Hu ZY, Parker RB, Herring VL, Laizure SC: Conventional liquid chromatography/triple quadrupole mass spectrometry based metabolite identification and semi-quantitative estimation approach in the investigation of in vitro dabigatran etexilate metabolism. Anal Bioanal Chem. 2013 Feb;405(5):1695-704. doi: 10.1007/s00216-012-6576-4. Epub 2012 Dec 14. [PubMed:23239178]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Ebner T, Wagner K, Wienen W: Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75. doi: 10.1124/dmd.110.033696. Epub 2010 Jun 15. [PubMed:20551237]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Glucuronosyltransferase activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Ebner T, Wagner K, Wienen W: Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75. doi: 10.1124/dmd.110.033696. Epub 2010 Jun 15. [PubMed:20551237]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xeno...
Gene Name
UGT2B15
Uniprot ID
P54855
Uniprot Name
UDP-glucuronosyltransferase 2B15
Molecular Weight
61035.815 Da
References
  1. Ebner T, Wagner K, Wienen W: Dabigatran acylglucuronide, the major human metabolite of dabigatran: in vitro formation, stability, and pharmacological activity. Drug Metab Dispos. 2010 Sep;38(9):1567-75. doi: 10.1124/dmd.110.033696. Epub 2010 Jun 15. [PubMed:20551237]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Nadph dehydrogenase (quinone) activity
Specific Function
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vi...
Gene Name
NQO2
Uniprot ID
P16083
Uniprot Name
Ribosyldihydronicotinamide dehydrogenase [quinone]
Molecular Weight
25918.4 Da
References
  1. Michaelis S, Marais A, Schrey AK, Graebner OY, Schaudt C, Sefkow M, Kroll F, Dreger M, Glinski M, Koester H, Metternich R, Fischer JJ: Dabigatran and dabigatran ethyl ester: potent inhibitors of ribosyldihydronicotinamide dehydrogenase (NQO2). J Med Chem. 2012 Apr 26;55(8):3934-44. doi: 10.1021/jm3001339. Epub 2012 Apr 17. [PubMed:22494098]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Galanis T, Thomson L, Palladino M, Merli GJ: New oral anticoagulants. J Thromb Thrombolysis. 2011 Apr;31(3):310-20. doi: 10.1007/s11239-011-0559-8. [PubMed:21327511]
  2. Scaglione F: New oral anticoagulants: comparative pharmacology with vitamin K antagonists. Clin Pharmacokinet. 2013 Feb;52(2):69-82. doi: 10.1007/s40262-012-0030-9. [PubMed:23292752]

Drug created on May 03, 2010 12:25 / Updated on November 14, 2018 12:54