Dabigatran ethyl ester

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H29N7O3
Molecular Weight	499.5643
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC(=O)CCN(C(=O)C1=CC2=C(C=C1)N(C)C(CNC3=CC=C(C=C3)C(N)=N)=N2)C4=NC=CC=C4

InChI

InChIKey=BGLLICFSSKPUMR-UHFFFAOYSA-N

InChI=1S/C27H29N7O3/c1-3-37-25(35)13-15-34(23-6-4-5-14-30-23)27(36)19-9-12-22-21(16-19)32-24(33(22)2)17-31-20-10-7-18(8-11-20)26(28)29/h4-12,14,16,31H,3,13,15,17H2,1-2H3,(H3,28,29)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24212379https://www.drugbank.ca/drugs/DB06695
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf https://www.pradaxa.com/

Dabigatran (Pradaxa, Prazaxa) is an anticoagulant medication that can be taken by mouth. FDA approved on October 19, 2010. 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. 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acyl coenzyme A:cholesterol acyltransferase 15 Target ID: CHEMBL2265 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24212379	Substrate 661
Thrombin 20 Target ID: CHEMBL204 Sources: https://www.drugbank.ca/drugs/DB06695 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf	Inhibitor 8297	1.2 nM [IC50]
Quinone reductase 2 12 Target ID: CHEMBL3959 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22494098 \|https://www.ncbi.nlm.nih.gov/pubmed/22494098	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Systemic embolism in patients with non-valvular atrial fibrillation 6 Sources: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf	Preventing	Approved 8429	PRADAXA Approved Use PRADAXA is a direct thrombin inhibitor indicated: To reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (1.1) For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days (1.2) To reduce the risk of recurrence of DVT and PE in patients who have been previously treated (1.3) For the prophylaxis of DVT and PE in patients who have undergone hip replacement surgery Launch Date 2010
Deep venous thrombosis 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf	Primary	Approved 8429	PRADAXA Approved Use PRADAXA is a direct thrombin inhibitor indicated: To reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (1.1) For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days (1.2) To reduce the risk of recurrence of DVT and PE in patients who have been previously treated (1.3) For the prophylaxis of DVT and PE in patients who have undergone hip replacement surgery Launch Date 2010
Pulmonary embolism 18 Sources: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf	Preventing	Approved 8429	PRADAXA Approved Use PRADAXA is a direct thrombin inhibitor indicated: To reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation (1.1) For the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) in patients who have been treated with a parenteral anticoagulant for 5-10 days (1.2) To reduce the risk of recurrence of DVT and PE in patients who have been previously treated (1.3) For the prophylaxis of DVT and PE in patients who have undergone hip replacement surgery Launch Date 2010
Unknown 2578

C_max

Value	Dose	Co-administered	Analyte	Population
348 ng/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/18399711/	150 mg 2 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DABIGATRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
2232 ng × h/mL REVIEW https://pubmed.ncbi.nlm.nih.gov/18399711/	150 mg 2 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DABIGATRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
11.3 h REVIEW https://pubmed.ncbi.nlm.nih.gov/18399711/	150 mg 2 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DABIGATRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
65% REVIEW https://pubmed.ncbi.nlm.nih.gov/18399711/	150 mg 2 times / day steady-state, oral dose: 150 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DABIGATRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 3 times / day single, oral Highest studied dose Dose: 400 mg, 3 times / day Route: oral Route: single Dose: 400 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17506785 Page: p.301	healthy, 18–45 n = 8 Health Status: healthy Age Group: 18–45 Sex: M Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/17506785 Page: p.301	Sources: https://pubmed.ncbi.nlm.nih.gov/17506785 Page: p.301
400 mg single, oral Highest studied dose Dose: 400 mg Route: oral Route: single Dose: 400 mg Sources: https://pubmed.ncbi.nlm.nih.gov/17506785 Page: p.301	healthy, 18–45 n = 6 Health Status: healthy Age Group: 18–45 Sex: M Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/17506785 Page: p.301	Sources: https://pubmed.ncbi.nlm.nih.gov/17506785 Page: p.301
150 mg 6 times / day multiple, oral Recommended Dose: 150 mg, 6 times / day Route: oral Route: multiple Dose: 150 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605	healthy, 18–45 n = 14 Health Status: healthy Age Group: 18–45 Sex: M+F Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605	Disc. AE: C-reactive protein increased, Alanine aminotransferase increase... AEs leading to discontinuation/dose reduction: C-reactive protein increased (7.14%) Alanine aminotransferase increase (7.14%) Haematuria (7.14%) Epistaxis (7.14%) Haemorrhoidal haemorrhage (7.14%) Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605
150 mg 2 times / day multiple, oral Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.5	unhealthy n = 6059 Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Population Size: 6059 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.5	Disc. AE: Bleeding, Gastrointestinal disorder NOS... AEs leading to discontinuation/dose reduction: Bleeding Gastrointestinal disorder NOS Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.5
150 mg 2 times / day multiple, oral Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.6	unhealthy n = 6059 Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Population Size: 6059 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.6	Disc. AE: Bleeding... AEs leading to discontinuation/dose reduction: Bleeding (grade 5, 0.07%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.6
150 mg 2 times / day multiple, oral (max) Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.1	Disc. AE: Spinal epidural hematoma, Bleeding... AEs leading to discontinuation/dose reduction: Spinal epidural hematoma Bleeding (grade 3-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
Alanine aminotransferase increase	7.14% Disc. AE	150 mg 6 times / day multiple, oral Recommended Dose: 150 mg, 6 times / day Route: oral Route: multiple Dose: 150 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605	healthy, 18–45 n = 14 Health Status: healthy Age Group: 18–45 Sex: M+F Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605
C-reactive protein increased	7.14% Disc. AE	150 mg 6 times / day multiple, oral Recommended Dose: 150 mg, 6 times / day Route: oral Route: multiple Dose: 150 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605	healthy, 18–45 n = 14 Health Status: healthy Age Group: 18–45 Sex: M+F Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605
Epistaxis	7.14% Disc. AE	150 mg 6 times / day multiple, oral Recommended Dose: 150 mg, 6 times / day Route: oral Route: multiple Dose: 150 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605	healthy, 18–45 n = 14 Health Status: healthy Age Group: 18–45 Sex: M+F Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605
Haematuria	7.14% Disc. AE	150 mg 6 times / day multiple, oral Recommended Dose: 150 mg, 6 times / day Route: oral Route: multiple Dose: 150 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605	healthy, 18–45 n = 14 Health Status: healthy Age Group: 18–45 Sex: M+F Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605
Haemorrhoidal haemorrhage	7.14% Disc. AE	150 mg 6 times / day multiple, oral Recommended Dose: 150 mg, 6 times / day Route: oral Route: multiple Dose: 150 mg, 6 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605	healthy, 18–45 n = 14 Health Status: healthy Age Group: 18–45 Sex: M+F Population Size: 14 Sources: https://pubmed.ncbi.nlm.nih.gov/32474728 Page: p.605
Bleeding	Disc. AE	150 mg 2 times / day multiple, oral Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.5	unhealthy n = 6059 Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Population Size: 6059 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.5
Gastrointestinal disorder NOS	Disc. AE	150 mg 2 times / day multiple, oral Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.5	unhealthy n = 6059 Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Population Size: 6059 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.5
Bleeding	grade 5, 0.07% Disc. AE	150 mg 2 times / day multiple, oral Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.6	unhealthy n = 6059 Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Population Size: 6059 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.6
Spinal epidural hematoma	Disc. AE	150 mg 2 times / day multiple, oral (max) Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.1
Bleeding	grade 3-5 Disc. AE	150 mg 2 times / day multiple, oral (max) Recommended Dose: 150 mg, 2 times / day Route: oral Route: multiple Dose: 150 mg, 2 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Non-valvular atrial fibrillation\|deep venous thrombosis\|pulmonary embolism Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022512s027lbl.pdf Page: p.1

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A 72 CYP2B6 810 CYP2C19 1478 CYP2E1 882 CYP4A11 21 P-gp 1461	CYP1A1 349 CYP1A2 1054 CYP2A6 543 CYP2B6 664 CYP2C19 991 CYP2E1 667 CYP4A11 119 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213 P-gp 1537	CYP2B6 547 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A 121	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP4A11 25	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=68, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: 68-69, (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no [IC50 >100 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=110 Page: (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 110	no
CYP2B6 1001	inducer 1573 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=110 Page: (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 110	no
CYP3A4 1925	inducer 1573 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=110 Page: (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 110	no
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=55, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=34, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=68 Page: 54-56, 56-57, (PMDA_A100_1 Japanese) 34, (PMDA_I100-_ Japanese) 68	no

Drug as victim

Target	Modality	Activity	Clinical evidence
CYP1A1 349	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no
CYP1A2 1054	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no
CYP2A6 543	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no
CYP2B6 664	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no
CYP2C19 991	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no
CYP2E1 667	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no
CYP4A11 119	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (PMDA_A100_1 Japanese) 32, (PMDA_I100-_ Japanese) 33	no
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT1A10 291	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT1A3 422	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT1A4 347	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT1A6 307	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT1A7 236	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT1A8 283	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT2B17 213	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
UGT2B4 249	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	no
CYP3A4 1737	substrate 3367 Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (ClinPharm) 13, (PMDA_A100_1 Japanese) 32, 40-41, (PMDA_I100_1 Japanese) 33	no	no (co-administration study) Comment: Coadministration of Atorvastatin (CYP3A4 & P-gp inhibitor, 400 mg QD x 4 days) with Dabigatran metexilate mesylate (150 mg BID x 3 days and 150 mg QD on Day 4) decreased total Dabigatran AUCtau,ss by 58% and Cmax,ss by 50%., Coadministration of Clarithromycin (CYP3A4 & P-gp inhibitor, 500 mg BID x 5 days & 500 mg QD on Day 6) with Dabigatran metexilate mesylate (150 mg QD on Day 6) increased total Dabigatran AUCinf by 19% and Cmax by 15%., Coadministration of Rifampicin (CYP3A4 & P-gp inducer, 600 mg QD x 7 days in the night) with Dabigatran metexilate mesylate (150 mg QD on Day 8 morning) decreased total Dabigatran AUCinf by 67% and Cmax by 66%., Coadministration of Ketoconazole (CYP3A4 & P-gp inhibitor, 400mg QD ) with Dabigatran metexilate mesylate (150 mg QD) increased total Dabigatran AUCinf by 138% and Cmax by 135%. Sources: https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=32, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=33 Page: (ClinPharm) 13, (PMDA_A100_1 Japanese) 32, 40-41, (PMDA_I100_1 Japanese) 33
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=55, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000ClinPharmR_Corrrected%203.11.2011.pdf#page=12, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000ClinPharmR_Corrrected%203.11.2011.pdf#page=34, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=66, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_K103_1.pdf#page=154 Page: 54-55, 56-57, (ClinPharm) 12, 13, 33-36, (PMDA_A100_1 Japanese) 33, 39, 40-41, (PMDA_I100_1 Japanese) 66, (PMDA_K103_1 Japanese) 152-156	no	no (co-administration study) Comment: Caco-2 cells, Efflux ratio = 1.09 (3 mcM), 0.95 (300 mcM); MDR1-LLC-PK1 cells, Efflux ratio = 1.35 (10 mcM); Coadministration of Amiodarone (P-gp & CYP2C9 inhibitor, 600 mg QD on Day 4) with Dabigatran metexilate mesylate (150 mg BID x 3 days and 150 mg QD on Day 4) increased total Dabigatran AUCtau,ss by 58% and Cmax by 50%., Coadministration of Verapamil (P-gp inhibitor, 120 mg single or multiple doses, or 240 mg single dose) with Dabigatran metexilate mesylate (150 mg single dose) increased total Dabigatran AUCinf by 39~143% and Cmax by 12~179%., Coadministration of Quinidine (200 mg every 2 hr x 5 on Day 3 (3 hr after the first Dabigatran dose), P-gp inhibitor) with Dabigatran metexilate mesylate (150 mg BID x 3 days (2nd dose on Day 3 was administrated 1 hr after the final Quinidine dose) increased total Dabigatran AUCtau,ss by 53% and Cmax,ss by 56%., Coadministration of Ketoconazole (CYP3A4 & P-gp inhibitor, 400mg QD ) with Dabigatran metexilate mesylate (150 mg QD) increased total Dabigatran AUCinf by 138% and Cmax by 135%., Coadministration of Atorvastatin (CYP3A4 & P-gp inhibitor, 400 mg QD x 4 days) with Dabigatran metexilate mesylate (150 mg BID x 3 days and 150 mg QD on Day 4) decreased total Dabigatran AUCtau,ss by 58% and Cmax,ss by 50%., Coadministration of Clarithromycin (CYP3A4 & P-gp inhibitor, 500 mg BID x 5 days & 500 mg QD on Day 6) with Dabigatran metexilate mesylate (150 mg QD on Day 6) increased total Dabigatran AUCinf by 19% and Cmax by 15%., Coadministration of Rifampicin (CYP3A4 & P-gp inducer, 600 mg QD x 7 days in the night) with Dabigatran metexilate mesylate (150 mg QD on Day 8 morning) decreased total Dabigatran AUCinf by 67% and Cmax by 66%. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=55, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000ClinPharmR_Corrrected%203.11.2011.pdf#page=12, https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000ClinPharmR_Corrrected%203.11.2011.pdf#page=34, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=66, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_K103_1.pdf#page=154 Page: 54-55, 56-57, (ClinPharm) 12, 13, 33-36, (PMDA_A100_1 Japanese) 33, 39, 40-41, (PMDA_I100_1 Japanese) 66, (PMDA_K103_1 Japanese) 152-156
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	yes [Km 371.4 uM]
UGT2B15 203	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	yes [Km 511.7 uM]
UGT2B7 389	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=70, https://www.pmda.go.jp/drugs/2011/P201100019/530353000_22300AMX00433000_A100_1.pdf#page=33, https://www.pmda.go.jp/drugs/2011/P201100019/53035300_22300AMX00433000_I100_1.pdf#page=101 Page: 70-71, (PMDA_A100_1 Japanese) 33, (PMDA_I100-_ Japanese) 101	yes [Km 987.3 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022512Orig1s000PharmR_Corrrected%203.11.2011.pdf#page=47 Page: 15, 47

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:70752	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:70752
ChemicalBook	CB61458206	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB61458206
MolPort	MolPort-008-155-829	https://www.molport.com/shop/molecule-link/MolPort-008-155-829
Selleck Chemicals	BIBR-953(Dabigatran)	http://www.selleckchem.com/products/BIBR-953(Dabigatran).html
ZINC	ZINC000001910616	http://zinc15.docking.org/substances/ZINC000001910616
eMolecules	31592368	https://www.emolecules.com/cgi-bin/more?vid=31592368

PubMed

Title	Date	PubMed
Peptidomimetic thrombin inhibitors.	2003 Sep-2004 Dec	15692265
Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I.	2004 Sep	15333033
Emerging anticoagulants: mechanism of action and future potential.	2006 Mar	16637459
Recent developments in antithrombotic therapy: will sodium warfarin be a drug of the past?	2006 Nov	18221095
Dabigatran versus enoxaparin after total hip replacement.	2007 Dec 15	18083398
Why differentiate low molecular weight heparins for venous thromboembolism?	2007 Jun 19	17578577
Dabigatran with or without concomitant aspirin compared with warfarin alone in patients with nonvalvular atrial fibrillation (PETRO Study).	2007 Nov 1	17950801
The new anticoagulants.	2007 Sep	17911567
The pharmacokinetics, pharmacodynamics and tolerability of dabigatran etexilate, a new oral direct thrombin inhibitor, in healthy male subjects.	2007 Sep	17506785
Brave new world: the current and future use of novel anticoagulants.	2008	18835010
Dabigatran etexilate.	2008	18681492
Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate.	2008	18399711
Pharmacokinetics and pharmacodynamics of the direct oral thrombin inhibitor dabigatran in healthy elderly subjects.	2008	18076218
[New anticoagulants].	2008 Feb	18278158
Update on atrial fibrillation: part I.	2008 Feb	18257025
The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans.	2008 Feb	18006647
[New oral anticoagulants: molecular characteristics, mechanisms of action, pharmacokinetics and pharmacodynamics].	2008 Nov	19087854
The prevention and treatment of venous thromboembolism with LMWHs and new anticoagulants.	2009	19707288
[New anticoagulants for secondary haemostasis--anti IIa inhibitors].	2009 Aug	19644604
Use of emerging oral anticoagulants in clinical practice: translating results from clinical trials to orthopedic and general surgical patient populations.	2009 Aug	19638915
Oral direct thrombin inhibitor AZD0837 for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation: a randomized dose-guiding, safety, and tolerability study of four doses of AZD0837 vs. vitamin K antagonists.	2009 Dec	19690349
Dabigatran versus warfarin in patients with atrial fibrillation.	2009 Dec 31	20050386
Dabigatran versus warfarin in patients with atrial fibrillation.	2009 Dec 31	20050385
Dabigatran versus warfarin in patients with atrial fibrillation.	2009 Dec 31	20042760
New anticoagulants: focus on venous thromboembolism.	2009 Jul	19601856
Dabigatran: new drug. Continue to use heparin, a better-known option.	2009 Jun	19637411
Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran.	2009 May	19376304
[Pharmacokinetics and pharmacodynamics of the new oral anticoagulants dabigatran and rivaroxaban].	2009 May-Jun	19712596
[Dabigatran and rivaroxaban, new oral anticoagulants for the treatment of venous thromboembolism].	2009 May-Jun	19712595
[The results of the RE-lY study promise more effective, safer and easier prevention of embolic complications in patients with non-valvular atrial fibrillation].	2009 Nov	20017441
Adherence to a new oral anticoagulant treatment prescription: dabigatran etexilate.	2009 Nov 3	19936159
Dabigatran versus warfarin in patients with atrial fibrillation.	2009 Sep 17	19717844
Oral antithrombotic inhibitors: dabigatran etexilate, meeting an unmet need?	2009 Sep-Oct	19706619
Pharmacology, pharmacokinetics, and pharmacodynamics of dabigatran etexilate, an oral direct thrombin inhibitor.	2009 Sep-Oct	19696042
[Dabigatran: a new therapeutic option for therapy and prophylaxis of thromboembolic diseases?].	2010 Feb	20104442
The new oral anticoagulants.	2010 Jan 7	19880491
Insights from the dabigatran versus warfarin in patients with atrial fibrillation (RE-LY) trial.	2010 Mar	20105114
Dabigatran and dabigatran ethyl ester: potent inhibitors of ribosyldihydronicotinamide dehydrogenase (NQO2).	2012 Apr 26	22494098

Patents

Sample Use Guides

In Vivo Use Guide

Unknown

Route of Administration: Unknown

In Vitro Use Guide

Unknown

Name

Type

Language

Dabigatran ethyl ester

Common Name

English

BIBR-951

Code

English

Dabigatran etexilate related compound B [USP]

Common Name

English

β-Alanine, N-[[2-[[[4-(aminoiminomethyl)phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl-, ethyl ester

Systematic Name

English

Ethyl 3-(2-(((4-carbamimidoylphenyl)amino)methyl)-1-methyl-N-(pyridin-2-yl)-1H-benzimidazole-5-carboxamido)propanoate

Systematic Name

English

BIBR0951

Code

English

BIBR-951CL

Code

English

Code System Code Type Description

FDA UNII

KJ4EH9410G

Created by admin on Sat Dec 16 08:04:38 GMT 2023 , Edited by admin on Sat Dec 16 08:04:38 GMT 2023

PRIMARY

CAS

429658-95-7

Created by admin on Sat Dec 16 08:04:38 GMT 2023 , Edited by admin on Sat Dec 16 08:04:38 GMT 2023

PRIMARY

EPA CompTox

DTXSID40332231

Created by admin on Sat Dec 16 08:04:38 GMT 2023 , Edited by admin on Sat Dec 16 08:04:38 GMT 2023

PRIMARY

PUBCHEM

446804

Created by admin on Sat Dec 16 08:04:38 GMT 2023 , Edited by admin on Sat Dec 16 08:04:38 GMT 2023

PRIMARY

ACTIVE MOIETY


					I0VM4M70GC

DABIGATRAN

SALT/SOLVATE (PARENT)


					EJ6LF8QCV8

Dabigatran ethyl ester mesylate

SALT/SOLVATE (PARENT)


					DBB8W334AN

DABIGATRAN ETHYL ESTER HYDROCHLORIDE

SUBSTANCE RECORD


					KJ4EH9410G

Dabigatran ethyl ester

Details

SMILES

InChI

DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/24212379https://www.drugbank.ca/drugs/DB06695Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf https://www.pradaxa.com/

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Approved Use

Launch Date

Approved Use

Launch Date

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/24212379https://www.drugbank.ca/drugs/DB06695
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf https://www.pradaxa.com/

C_max

T_1/2

F_unbound

Drug as perpetrator