DABIGATRAN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C25H25N7O3
Molecular Weight	471.5111
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1C(CNC2=CC=C(C=C2)C(N)=N)=NC3=C1C=CC(=C3)C(=O)N(CCC(O)=O)C4=NC=CC=C4

InChI

InChIKey=YBSJFWOBGCMAKL-UHFFFAOYSA-N

InChI=1S/C25H25N7O3/c1-31-20-10-7-17(25(35)32(13-11-23(33)34)21-4-2-3-12-28-21)14-19(20)30-22(31)15-29-18-8-5-16(6-9-18)24(26)27/h2-10,12,14,29H,11,13,15H2,1H3,(H3,26,27)(H,33,34)

HIDE SMILES / InChI

Molecular Formula	C25H25N7O3
Molecular Weight	471.5111
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.drugbank.ca/drugs/DB06695https://www.ncbi.nlm.nih.gov/pubmed/24212379
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 ethyl ester is a one of the intermediate, which is formed during metabolic reactions from dabigatran etexilate. Dabigatran ethyl ester forming under the action of intestinal carboxylesterase 2 (CES2) further is hydrolyzed by CES1 with formation of active drug, thrombin inhibitor, dabigatranand. Dabigatran ethyl ester is a much stronger inhibitor of ribosyldihydronicotinamide dehydrogenase, than dabigatran.

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 656
Thrombin 20 Target ID: CHEMBL204 Sources: https://www.drugbank.ca/drugs/DB06695 \| http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf	Inhibitor 8228	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 8228

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 8360	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 1.28735995E12
Deep venous thrombosis 6 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022512s007lbl.pdf	Primary	Approved 8360	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 1.28735995E12
Pulmonary embolism 18 Sources: http://docs.boehringer-ingelheim.com/Prescribing%20Information/PIs/Pradaxa/Pradaxa.pdf	Preventing	Approved 8360	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 1.28735995E12
Unknown 2565

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 1709 inhibitor 1579 inducer 768	inhibitor 1752	inhibitor 1837	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A 72 CYP2B6 799 CYP2C19 1463 CYP2E1 876 CYP4A11 21 P-gp 1437	CYP1A1 348 CYP1A2 1032 CYP2A6 523 CYP2B6 660 CYP2C19 985 CYP2E1 648 CYP4A11 102 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 290 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213 P-gp 1527	CYP2B6 538 CYP1A2 689

Drug as perpetrator

Target	Modality	Activity
CYP1A 121	inhibitor 3240 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 985	inhibitor 3240 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 1537	inhibitor 3240 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 1803	inhibitor 3240 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 1875	inhibitor 3240 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 964	inhibitor 3240 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 1909	inhibitor 3240 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 3240 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 1673	inducer 1542 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 985	inducer 1542 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 1909	inducer 1542 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 1626	inhibitor 3240 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 348	substrate 3326 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 1032	substrate 3326 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 523	substrate 3326 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 660	substrate 3326 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 985	substrate 3326 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 648	substrate 3326 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 102	substrate 3326 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 3326 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 290	substrate 3326 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 3326 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 3326 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 3326 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 3326 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 3326 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 3326 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 3326 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 1709	substrate 3326 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 1527	substrate 3326 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 3326 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 3326 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 3326 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 1632	inhibitor 1613 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
Structure-based design of novel potent nonpeptide thrombin inhibitors.	2002 Apr 25	11960487
Investigational treatments of venous thromboembolism.	2007 Apr	17371192
Effects of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate, on thrombus formation and bleeding time in rats.	2007 Aug	17721615
Anithrombotic prevention in vascular disease: bases for a new strategy in antithrombotic therapy.	2007 Aug 29	17727726
Dabigatran versus enoxaparin after total hip replacement.	2007 Dec 15	18083398
In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate.	2007 Jul	17598008
Population pharmacokinetic analysis of the new oral thrombin inhibitor dabigatran etexilate (BIBR 1048) in patients undergoing primary elective total hip replacement surgery.	2007 Mar	17322149
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
Emergence of new oral antithrombotics: a critical appraisal of their clinical potential.	2008	19337550
New issues in oral anticoagulants.	2008	19074093
[Perioperative venous thromboembolism prophylaxis: short review and recommendations].	2008 Dec	19185783
[New anticoagulants].	2008 Feb	18278158
The metabolism and disposition of the oral direct thrombin inhibitor, dabigatran, in humans.	2008 Feb	18006647
New oral anticoagulants in atrial fibrillation.	2008 Jan	18096568
Controversies in the antiphospholipid syndrome: can we ever stop warfarin?	2008 Nov 11	19014462
New developments in anticoagulation for atrial fibrillation.	2008 Sep	18814828
[Dabigatran versus Warfarin in patients with atrial fibrillation. Results of the RE-LY study].	2009	19845524
A cost-effectiveness model comparing rivaroxaban and dabigatran etexilate with enoxaparin sodium as thromboprophylaxis after total hip and total knee replacement in the irish healthcare setting.	2009	19803538
The prevention and treatment of venous thromboembolism with LMWHs and new anticoagulants.	2009	19707288
Use of anticoagulants in elderly patients: practical recommendations.	2009	19503778
Favorable therapeutic index of the direct factor Xa inhibitors, apixaban and rivaroxaban, compared with the thrombin inhibitor dabigatran in rabbits.	2009 Aug	19500242
[New oral anticoagulants. Consequences for perioperative coagulation diagnostics and therapy].	2009 Dec	19823782
Dabigatran versus warfarin in the treatment of acute venous thromboembolism.	2009 Dec 10	19966341
Dabigatran versus warfarin in patients with atrial fibrillation.	2009 Dec 31	20050385
Dabigatran versus warfarin in patients with atrial fibrillation.	2009 Dec 31	20050384
Dabigatran versus warfarin in patients with atrial fibrillation.	2009 Dec 31	20050383
New anticoagulants: focus on venous thromboembolism.	2009 Jul	19601856
Dabigatran: new drug. Continue to use heparin, a better-known option.	2009 Jun	19637411
[Venous thromboembolism prophylaxis in orthopaedics and traumatology].	2009 Mar	19378847
The prevention of hospital-acquired venous thromboembolism in the United Kingdom.	2009 Mar	19076173
Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran.	2009 May	19376304
Rivaroxaban -- an oral, direct Factor Xa inhibitor: lessons from a broad clinical study programme.	2009 May	19187276
[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
Dabigatran, a direct thrombin inhibitor, demonstrates antifibrotic effects on lung fibroblasts.	2009 Nov	19877031
The RE-LY study: Randomized Evaluation of Long-term anticoagulant therapY: dabigatran vs. warfarin.	2009 Nov	19770196
Dabigatran etexilate in venous thromboembolism.	2009 Oct	20069135
[New developments in antithrombotic care].	2009 Sep	19899386
Dabigatran enhances clot susceptibility to fibrinolysis by mechanisms dependent on and independent of thrombin-activatable fibrinolysis inhibitor.	2010 Apr	20088944
New oral anticoagulants: a practical guide for clinicians.	2010 Feb	19888552
The new oral anticoagulants.	2010 Jan 7	19880491
Comparative efficacy and safety of the novel oral anticoagulants dabigatran, rivaroxaban and apixaban in preclinical and clinical development.	2010 Mar	20135071

Patents

Sample Use Guides

In Vivo Use Guide

Usual Adult Dose for Deep Vein Thrombosis - Prophylaxis Recommended doses: 150 mg orally twice a day Usual Adult Dose for Prevention of Thromboembolism in Atrial Fibrillation Recommended doses: 150 mg orally twice a day Usual Adult Dose for Deep Vein Thrombosis/Pulmonary Embolism Prophylaxis Following Hip Replacement Surgery 110 mg orally 1 to 4 hours after surgery and after hemostasis has been achieved, then 220 mg orally once a day for 28 to 35 days

Route of Administration: Oral

In Vitro Use Guide

Dabigatran at higher concentrations (500 and 1000 nM) potently inhibited thrombus formation. In platelet-poor plasma, dabigatran at 250 and 500 nM efficiently prolonged the lag time (LT) and moderately reduce peak height (PH) of TG.

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:40:48 UTC 2023` Edited by `admin` on `Wed Jul 05 23:40:48 UTC 2023`
Record UNII	I0VM4M70GC
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

DABIGATRAN

Official Name

English

BIBR 953 ZW

Code

English

BIBR-953-ZW

Code

English

N-((2-((P-AMIDINOANILINO)METHYL)-1-METHYL-5-BENZIMIDAZOLYL)CARBONYL)-N-2-PYRIDYL-.BETA.-ALANINE

Common Name

English

DABIGATRAN [USAN]

Common Name

English

3-{[(2-{[(4-Carbamimidoylphenyl)amino]methyl}-1-methyl-1H-benzimidazol-5-yl)carbonyl](pyridin-2-yl)amino}propanoic acid

Systematic Name

English

DABIGATRAN [MART.]

Common Name

English

dabigatran [INN]

Common Name

English

DABIGATRAN [VANDF]

Common Name

English

.BETA.-ALANINE, N-((2-(((4-(AMINOIMINOMETHYL)PHENYL)AMINO)METHYL)-1-METHYL-1H-BENZIMIDAZOL-5-YL)CARBONYL)-N-2-PYRIDINYL-

Systematic Name

English

DABIGATRAN [MI]

Common Name

English

PRADAXA (DABIGATRAN)

Brand Name

English

BIBR-953

Code

English

Dabigatran [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C263