CLOPIDOGREL BESYLATE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H16ClNO2S.C6H6O3S
Molecular Weight	479.997
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OS(=O)(=O)C1=CC=CC=C1.COC(=O)[C@@H](N2CCC3=C(C2)C=CS3)C4=CC=CC=C4Cl

InChI

InChIKey=CUZIJKLLBDXNFV-RSAXXLAASA-N

InChI=1S/C16H16ClNO2S.C6H6O3S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14;7-10(8,9)6-4-2-1-3-5-6/h2-5,7,9,15H,6,8,10H2,1H3;1-5H,(H,7,8,9)/t15-;/m0./s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdf | https://www.drugbank.ca/drugs/DB00758 | https://www.ncbi.nlm.nih.gov/pubmed/15199474

Clopidogrel, an antiplatelet agent structurally and pharmacologically similar to ticlopidine, is used to inhibit blood clots in a variety of conditions such as peripheral vascular disease, coronary artery disease, and cerebrovascular disease. Clopidogrel is sold under the name Plavix by Sanofi and Bristol-Myers Squibb. Plavix (clopidogrel bisulfate) is an inhibitor of ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADPmediated activation of the glycoprotein GPIIb/IIIa complex. Clopidogrel must be metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor and the subsequent ADPmediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible. Consequently, platelets exposed to clopidogrel’s active metabolite are affected for the remainder of their lifespan (about 7 to 10 days). Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the amplification of platelet activation by released ADP. Plavix (clopidogrel bisulfate) is indicated for the reduction of atherothrombotic events.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Purinergic receptor P2Y12 23 Target ID: CHEMBL2001 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15199474 \| https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdf \| https://www.drugbank.ca/drugs/DB00758	Antagonist 2778		6.9 null [pKi]
Purinergic receptor P2Y12 23 Target ID: CHEMBL2001 Sources: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=0078fb3d-3595-4ae1-a059-1d5e81c879cf&type=display\|https://www.ncbi.nlm.nih.gov/pubmed/10446085	Antagonist 2778

Conditions

Condition	Modality	Highest Phase	Product
Atherosclerosis 74 Sources: https://www.drugs.com/pro/clopidogrel.html	Primary	Approved 8429	PLAVIX Approved Use Plavix (clopidogrel bisulfate) is indicated for the reduction of atherothrombotic events as follows: • Recent MI, Recent Stroke or Established Peripheral Arterial Disease For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death. • Acute Coronary Syndrome -For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/nonQ-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI, or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia. Plavix (clopidogrel bisulfate) is indicated for the reduction of atherothrombotic events as follows: • Recent MI, Recent Stroke or Established Peripheral Arterial Disease For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death. • Acute Coronary Syndrome -For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/nonQ-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI, or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia. Launch Date 1997
Acute coronary syndrome 33 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdf	Primary	Approved 8429	PLAVIX Approved Use Plavix (clopidogrel bisulfate) is indicated for the reduction of atherothrombotic events as follows: • Recent MI, Recent Stroke or Established Peripheral Arterial Disease For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death. • Acute Coronary Syndrome -For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/nonQ-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI, or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia. Launch Date 1997
Peripheral arterial disease 22 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdf	Primary	Approved 8429	PLAVIX Approved Use Plavix (clopidogrel bisulfate) is indicated for the reduction of atherothrombotic events as follows: • Recent MI, Recent Stroke or Established Peripheral Arterial Disease For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death. • Acute Coronary Syndrome -For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/nonQ-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI, or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia. Launch Date 1997
Myocardial infarction 121 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdf	Preventing	Approved 8429	PLAVIX Approved Use Plavix (clopidogrel bisulfate) is indicated for the reduction of atherothrombotic events as follows: • Recent MI, Recent Stroke or Established Peripheral Arterial Disease For patients with a history of recent myocardial infarction (MI), recent stroke, or established peripheral arterial disease, Plavix has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (fatal or not), and other vascular death. • Acute Coronary Syndrome -For patients with non-ST-segment elevation acute coronary syndrome (unstable angina/nonQ-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG, Plavix has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI, or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke, or refractory ischemia. Launch Date 1997

C_max

Value	Dose	Analyte	Population
1500 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	75 mg 1 times / day multiple, oral dose: 75 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
15800 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2520 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	75 mg 1 times / day multiple, oral dose: 75 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4600 pg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.521 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02185534	75 mg single, oral dose: 75 mg route of administration: oral experiment type: single co-administered:	CLOPIDOGREL plasma	Homo sapiens population: healthy age: sex: food status:

AUC

Value	Dose	Analyte	Population
3130 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	75 mg 1 times / day multiple, oral dose: 75 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
50600 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7440 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	75 mg 1 times / day multiple, oral dose: 75 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
9890 pg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.767 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02185534	75 mg single, oral dose: 75 mg route of administration: oral experiment type: single co-administered:	CLOPIDOGREL plasma	Homo sapiens population: healthy age: sex: food status:
1.09 ng*h/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT02185534	75 mg single, oral dose: 75 mg route of administration: oral experiment type: single co-administered:	CLOPIDOGREL plasma	Homo sapiens population: healthy age: sex: food status:

T_1/2

Value	Dose	Analyte	Population
8.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	75 mg 1 times / day multiple, oral dose: 75 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	75 mg 1 times / day multiple, oral dose: 75 mg route of administration: Oral experiment type: MULTIPLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
7.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/22128201	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:	CLOPIDOGREL BISULFATE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020839s044lbl.pdf	unknown, unknown		CLOPIDOGREL BISULFATE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
600 mg 1 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26063503	healthy, 20-45 years n = 27 Health Status: healthy Age Group: 20-45 years Sex: M Population Size: 27 Sources: https://pubmed.ncbi.nlm.nih.gov/26063503	Other AEs: Uric acid abnormal... Other AEs: Uric acid abnormal (5 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/26063503
1650 mg single, oral Overdose Dose: 1650 mg Route: oral Route: single Dose: 1650 mg Co-administed with:: phenytoin sodium(1400 mg; single) simvastatin(120 mg; single) Sources: https://pubmed.ncbi.nlm.nih.gov/17286151	unknown, 49 years n = 1 Health Status: unknown Age Group: 49 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/17286151	Sources: https://pubmed.ncbi.nlm.nih.gov/17286151
600 mg 1 times / day multiple, oral (starting) Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16878371	unhealthy, 59 years n = 1 Health Status: unhealthy Age Group: 59 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/16878371	Disc. AE: Transaminases increased, Fever... AEs leading to discontinuation/dose reduction: Transaminases increased (1 patient) Fever (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/16878371

AEs

AE	Significance	Dose	Population
Uric acid abnormal	5 patients	600 mg 1 times / day multiple, oral (starting) Highest studied dose Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26063503	healthy, 20-45 years n = 27 Health Status: healthy Age Group: 20-45 years Sex: M Population Size: 27 Sources: https://pubmed.ncbi.nlm.nih.gov/26063503
Fever	1 patient Disc. AE	600 mg 1 times / day multiple, oral (starting) Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16878371	unhealthy, 59 years n = 1 Health Status: unhealthy Age Group: 59 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/16878371
Transaminases increased	1 patient Disc. AE	600 mg 1 times / day multiple, oral (starting) Dose: 600 mg, 1 times / day Route: oral Route: multiple Dose: 600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16878371	unhealthy, 59 years n = 1 Health Status: unhealthy Age Group: 59 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/16878371

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:37941	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:37941
MolPort	MolPort-002-885-817	https://www.molport.com/shop/molecule-link/MolPort-002-885-817
ZINC	ZINC000034781704	http://zinc15.docking.org/substances/ZINC000034781704
eMolecules	2735330	https://www.emolecules.com/cgi-bin/more?vid=2735330

PubMed

Title	Date	PubMed
Drug-induced thrombotic microangiopathy: incidence, prevention and management.	2001	11444722
Benefit of ADP receptor antagonists in atherothrombotic patients: new evidence.	2001	11316916
Novel platelet inhibitors.	2001	11160773
Clinical application of procedural platelet monitoring during percutaneous coronary intervention among patients at increased bleeding risk.	2001 Apr	11406730
Regular or "super-aspirins"? A review of thienopyridines or aspirin to prevent stroke.	2001 Apr	11347797
Results of CURE trial for acute coronary syndrome.	2001 Apr 11	11308379
[Acute heart attacks. Prognosis can be further improved].	2001 Apr 5	11340908
Deaggregation is an integral component of the response of platelets to ADP in vitro: kinetic studies of literature and original data.	2001 Aug	11487380
Radiation-induced glomerular thrombus formation and nephropathy are not prevented by the ADP receptor antagonist clopidogrel.	2001 Aug 1	11483346
Bench to bedside: the development of rapamycin and its application to stent restenosis.	2001 Aug 21	11514367
Severe hypersensitivity associated with clopidogrel.	2001 Aug 21	11511158
Acute myocardial infarction 2000 treatment.	2001 Fall	11569324
Antiplatelet therapy in the elderly. Aspirin, ticlopidine-clopidogrel, and GPIIb/GPIIIa antagonists.	2001 Feb	11270132
Combination therapy with aspirin plus clopidogrel versus aspirin plus ticlopidine for prevention of subacute thrombosis after successful native coronary stenting.	2001 Feb 15	11179539
[Clopidogrel? Known or known?].	2001 Jan	11223636
Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery.	2001 Jan 23	11157686
Localized intracoronary gamma-radiation therapy to inhibit the recurrence of restenosis after stenting.	2001 Jan 25	11172151
Clopidogrel (Plavix): hematological reactions.	2001 Jan 9	11202680
[Can we use clopidogrel in patients with coronary stent?].	2001 Jan-Mar	11488209
ADP receptors of platelets and their inhibition.	2001 Jul	11487010
Multiple intracranial aneurysms as delayed complications of an atrial myxoma: case report.	2001 Jul	11440443
Acute coronary syndrome: are intervention and IIb/IIIa platelet inhibitors epiphenomena?	2001 Jul-Aug	11501219
[Toxic skin reaction to clopidogrel].	2001 Jun	11431626
Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs.	2001 Jun	11413167
Incidence of thrombotic occlusion and major adverse cardiac events between two and four weeks after coronary stent placement: analysis of 5,678 patients with a four-week ticlopidine regimen.	2001 Jun 15	11419889
Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization.	2001 Jun 21	11419425
[Pharmacy clinics. Medication of the month. Clopidogrel (Plavix)].	2001 Mar	11338792
[New platelet inhibitors].	2001 Mar	11315485
Activation of Gi-coupled receptors releases a tonic state of inhibited platelet aggregation.	2001 Mar	11297037
Initial experience with a newer generation coronary stent.	2001 Mar	11231647
New recommendations from the 1999 American College of Cardiology/American Heart Association acute myocardial infarction guidelines.	2001 May	11346067
Orbofiban: an orally active GPIIb/IIIa platelet receptor antagonist.	2001 May	11301411
Edge stenosis after intracoronary radiotherapy: angiographic, intravascular, and histological findings.	2001 May 1	11331266
Clopidogrel and aplastic anaemia.	2001 May 5	11360950
Coronary stent deployment in situs inversus.	2001 Nov	11602566
[Clopidogrel in acute coronary syndromes with non-ST elevation. Clinical implications of the CURE trial].	2001 Oct	11591313
Prevention of venous graft sclerosis with clopidogrel and aspirin combined with a mesh tubing in a dog model of arteriovenous bypass grafting.	2001 Oct	11563893
Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.	2001 Sep	11604563
Cilostazol for prevention of thrombosis and restenosis after intracoronary stenting.	2001 Sep	11573862
Thrombotic thrombocytopenic purpura associated with clopidogrel administration: case report and brief review.	2001 Sep	11570785
Effects of combining three different antiplatelet agents on platelets and leukocytes in whole blood in vitro.	2001 Sep	11564653
Effect of clopidogrel added to aspirin before percutaneous coronary intervention on the risk associated with C-reactive protein.	2001 Sep 15	11564394

Patents

Sample Use Guides

In Vivo Use Guide

Recent MI, Recent Stroke, or Established Peripheral Arterial Disease The recommended daily dose of is 75 mg once daily.

Route of Administration: Oral

In Vitro Use Guide

Incubation of human washed platelets with clopidogrel resulted in a time- (maximum effects after 30 min) and concentration-dependent (IC50 1.9+/-0.3 uM) inhibition of ADP (6 uM)-induced platelet aggregation. Clopidogrel (30 uM) did not inhibit collagen (2.5 ug ml(-1))-, U46619 (1 uM)- or thrombin (0.1 u ml(-1))-induced platelet aggregation.

Name

Type

Language

CLOPIDOGREL BESILATE

Preferred Name

English

CLOPIDOGREL BESYLATE

Common Name

English

CLOPIDOGREL APOTEX

Brand Name

English

CLOPIDOGREL BENZENESULFONIC ACID SALT

Common Name

English

CLOPIDOGREL ACINO PHARMA GMBH

Brand Name

English

CLOPIDOGREL ACINO PHARMA

Brand Name

English

CLOPIDOGREL RATIOPHARM GMBH

Brand Name

English

CLOPIDOGREL HEXAL

Brand Name

English

CLOPIDOGREL ACINO

Brand Name

English

GREPID

Brand Name

English

CLOPIDOGREL SANDOZ

Brand Name

English

CLOPIDOGREL 1A-PHARMA

Brand Name

English

Clopidogrel Besylate [WHO-DD]

Common Name

English

CLOPIDOGREL BENZENESULFONATE

Common Name

English

CLOPIDOGREL BESILATE [EP MONOGRAPH]

Common Name

English

THIENO(3,2-C)PYRIDINE-5(4H)-ACETIC ACID, .ALPHA.-(2-CHLOROPHENYL)-6,7-DIHYDRO-, METHYL ESTER, (.ALPHA.S)-, BENZENESULFONATE

Common Name

English

CLOPIDOGREL-RATIOPHARM

Brand Name

English

CLOPIDOGREL BESILATE [EMA EPAR]

Common Name

English

(S)-METHYL-2-(2-CHLOROPHENYL)-2-(6,7-DIHYDROTHIENO(3,2-C)PYRIDIN-5(4H)-YL)ACETATE METHANESULFONATE

Systematic Name

English

THIENO(3,2-C)PYRIDINE-5(4H)-ACETIC ACID, .ALPHA.-(2-CHLOROPHENYL)-6,7-DIHYDRO-, METHYL ESTER, (.ALPHA.S)-, BENZENESULFONATE (1:1)

Common Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

CLOPIDOGRAL HEXAL (WITHDRAWN: MYOCARDIAL INFARCTION)