Clopidogrel
Systematic (IUPAC) name
(+)-(S)-methyl 2-(2-chlorophenyl)- 2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate
Identifiers
CAS number	113665-84-2
ATC code	B01AC04
PubChem	60606
DrugBank	APRD00444
Chemical data
Formula	C16H16ClNO2S
Mol. mass	321.82 g/mol
Pharmacokinetic data
Bioavailability	>50%
Protein binding	94–98%
Metabolism	Hepatic
Half life	7–8 hours (inactive metabolite)
Excretion	50% renal 46% biliary
Therapeutic considerations
Pregnancy cat.	B1(AU) B(US) Image File history File links Clopidogrel. ... Image File history File links Size of this preview: 800 × 578 pixelsFull resolution (1000 × 722 pixel, file size: 155 KB, MIME type: image/png) File historyClick on a date/time to view the file as it appeared at that time. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... This article or section does not cite any references or sources. ... General Name, symbol, number carbon, C, 6 Chemical series nonmetals Group, period, block 14, 2, p Appearance black (graphite) colorless (diamond) Standard atomic weight 12. ... General Name, Symbol, Number hydrogen, H, 1 Chemical series nonmetals Group, Period, Block 1, 1, s Appearance colorless Atomic mass 1. ... General Name, symbol, number chlorine, Cl, 17 Chemical series halogens Group, period, block 17, 3, p Appearance yellowish green Standard atomic weight 35. ... General Name, Symbol, Number nitrogen, N, 7 Chemical series nonmetals Group, Period, Block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, Symbol, Number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless (gas) very pale blue (liquid) Standard atomic weight 15. ... General Name, Symbol, Number sulfur, S, 16 Chemical series nonmetals Group, Period, Block 16, 3, p Appearance lemon yellow Standard atomic weight 32. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... A drugs efficacy may be affected by the degree to which it binds to the proteins within blood plasma. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The liver is an organ present in vertebrates and some other animals. ... It has been suggested that Effective half-life be merged into this article or section. ... Excretion is the process of eliminating waste products of metabolism and other materials that are of no use. ... Kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... X-Ray of the bile duct during a laprascopic cholecystectomy A bile duct is any of a number of long tube-like structures that carry bile. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... For other uses, see Australia (disambiguation). ... Motto: (Out Of Many, One) (traditional) In God We Trust (1956 to date) Anthem: The Star-Spangled Banner Capital Washington D.C. Largest city New York City None at federal level (English de facto) Government Federal constitutional republic  - President George Walker Bush (R)  - Vice President Dick Cheney (R) Independence from...
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Routes	Oral

A box of Plavix

Clopidogrel is a potent oral antiplatelet agent often used in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. In 2006, generic clopidogrel was briefly marketed by Apotex, a Canadian generic pharmaceutical company before a court order halted further production until resolution of a patent infringement case brought by Bristol-Myers Squibb.^[1] The court ruled that Bristol-Myers Squibb's patent was valid and has patent protection until November 2011.^[2] In 2007, the production was halted to many retail pharmacies and will be changing back to Plavix. In 2005 it was reported that Plavix was the world's second highest selling pharmaceutical with sales of US$5.9 billion.^[3] In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body 1. ... Image File history File links Metadata Size of this preview: 800 × 600 pixelsFull resolution (3648 × 2736 pixel, file size: 6. ... Image File history File links Metadata Size of this preview: 800 × 600 pixelsFull resolution (3648 × 2736 pixel, file size: 6. ... An antiplatelet drug is a member of a class of pharmaceuticals that decreases platelet aggregation and inhibits thrombus formation. ... Coronary heart disease (CHD), also called coronary artery disease (CAD) and atherosclerotic heart disease, is the end result of the accumulation of atheromatous plaques within the walls of the arteries that supply the myocardium (the muscle of the heart). ... Peripheral vascular disease (PVD) is a disease in the large blood vessels of the arms, legs, and feet. ... Cerebrovascular disease is damage to the blood vessels in the brain, resulting in a stroke. ... Bristol-Myers Squibb (NYSE: BMY), colloquially referred to as BMS, is a pharmaceutical corporation, formed by a 1989 merger between pharmaceutical companies Bristol-Myers Company, founded in 1887 by William McLaren Bristol and John Ripley Myers in Clinton, NY (both were graduates of Hamilton College), and Squibb Corporation. ... Sanofi-aventis (Euronext: SAN, NYSE: SNY), headquartered in Paris, France, is one of the 3 largest pharmaceutical companies in the world, along with Pfizer,GlaxoSmithKline. ... A trade name, also known as a trading name or a business name, is the legal name of a business, or the name which a business trades under for commercial purposes. ... Apotex is a Canadian pharmaceutical corporation. ... A pharmaceutical company, or drug company, is a commercial business whose focus is to research, develop, market and/or distribute drugs, most commonly in the context of healthcare. ... Bristol-Myers Squibb (NYSE: BMY), colloquially referred to as BMS, is a pharmaceutical corporation, formed by a 1989 merger between pharmaceutical companies Bristol-Myers Company, founded in 1887 by William McLaren Bristol and John Ripley Myers in Clinton, NY (both were graduates of Hamilton College), and Squibb Corporation. ...

Pharmacology

The mechanism of action of clopidogrel is irreversible blockade of the adenosine diphosphate (ADP) receptor on platelet cell membranes. This receptor is named P2Y12 and is important in platelet aggregation, the cross-linking of platelets by fibrin. The blockade of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa pathway. Adenosine diphosphate, abbreviated ADP, is a nucleotide. ... A 250 ml bag of newly collected platelets. ... The introduction to this article provides insufficient context for those unfamiliar with the subject matter. ... Fibrin is a protein involved in the clotting of blood. ... In medicine, glycoprotein IIb/IIIa, also gpIIb/IIIa, is an integrin found on platelets. ...

Platelet inhibition can be demonstrated two hours after a single dose of oral clopidogrel, but the onset of action is slow, so that a loading-dose of 300-600 mg is usually administered.

Clinical use

Indications

Clopidogrel is indicated for:^[4]

• Prevention of vascular ischaemic events in patients with symptomatic atherosclerosis
• Acute coronary syndrome without ST-segment elevation (NSTEMI), along with aspirin

It is also used, along with aspirin, for the prevention of thromboembolism after placement of intracoronary stent. ^[4] In medicine, ischemia (Greek ισχαιμία, isch- is restriction, hema or haema is blood) is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. ... Acute myocardial infarction (AMI or MI), more commonly known as a heart attack, is a disease state that occurs when the blood supply to a part of the heart is interrupted. ...

Most consensus-based therapeutic guidelines recommend the use of clopidogrel, over aspirin, in patients requiring antiplatelet therapy but with a history of gastric ulceration, as inhibition of the synthesis of prostaglandins by aspirin (acetylsalicylic acid) can exacerbate this condition. A recent study has shown that in patients with healed aspirin-induced ulcers, however, patients receiving aspirin plus the proton pump inhibitor esomeprazole had a lower incidence of recurrent ulcer bleeding than patients receiving clopidogrel. ^[5] Aspirin, or acetylsalicylic acid (IPA: ), (acetosal) is a drug in the family of salicylates, often used as an analgesic (to relieve minor aches and pains), antipyretic (to reduce fever), and as an anti-inflammatory. ... Proton pump inhibitors (or PPIs) are a group of drugs whose main action is pronounced and long-lasting reduction of gastric acid production. ... Esomeprazole is a proton pump inhibitor used in the treatment of dyspepsia, peptic ulcer disease (PUD), GERD and Zollinger-Ellison syndrome. ...

Dosage forms

Clopidogrel is marketed as clopidogrel bisulfate (clopidogrel hydrogen sulfate), most commonly under the trade names Plavix or Iscover, as 75 mg oral tablets.

Pharmacokinetics and Metabolism

After repeated 75-mg oral doses of clopidogrel (base), plasma concentrations of the parent compound, which has no platelet inhibiting effect, are very low and are generally below the quantification limit (0.000258 mg/L) beyond 2 hours after dosing. Clopidogrel is extensively metabolized by the liver. The main circulating metabolite is the carboxylic acid derivative, and it too has no effect on platelet aggregation. It represent about 85% of the circulating drug-related compound in plasma.

Following an oral dose of ¹⁴C-labeled clopidogrel in humans, approximately 50% was excreted in the urine and approximately 46% in the feces in the 5 days after dosing. The elimination half-life of the main circulating metabolite was 8 hours after single and repeated administration. Covalent binding to platelets accounted for 2% of radiolabel with a half-life of 11 days. Effect of Food: Administration of PLAVIX (clopidogrel bisulfate) with meals did not significantly modify the bioavailability of clopidogrel as assessed by the pharmacokinetics of the main circulating metabolite. Half-Life For a quantity subject to exponential decay, the half-life is the time required for the quantity to fall to half of its initial value. ...

Absorption and Distribution: Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg clopidogrel (base), with peak plasma levels (appx. 3 mg/L) of the main circulating metabolite occurring approximately 1 hour after dosing. The pharmacokinetics of the main circulating metabolite are linear (plasma concentrations increased in proportion to does) in the dose range of 50 to 150 mg of clopidogrel. Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites. Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma proteins (98% and 94%, respectively). The binding is nonsaturable in vitro up to a concentration of 110 μg/mL.

Metabolism and Elimination: In vitro and in vivo, clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative. In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed. Structure of a carboxylic acid The 3D structure of the carboxyl group A space-filling model of the carboxyl group Carboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -C(=O)OH, usually written -COOH or -CO2H. [1] Carboxylic acids are Bronsted...

Adverse effects

Serious adverse drug reactions associated with clopidogrel therapy include: An adverse drug reaction (abbreviated ADR) is a term to describe the unwanted, negative consequences sometimes associated with the use of medications. ...

• Severe neutropenia (Incidence: 5/10,000)
• Thrombotic thrombocytopenic purpura (TTP) (Incidence: 4/1,000,000 patients treated)
• Hemorrhage - The incidence of hemorrhage may be increased by the co-administration of aspirin.
  • Gastrointestinal Hemorrhage (Incidence: 2.0%)
  • Cerebral Hemorrhage (Incidence: 0.1 to 0.4%)
• Erectile Dyfunction (Incidence as yet unknown)

Neutropenia (or neutropaenia, adjective neutrop(a)enic) is a hematological disorder characterized by an abnormally low number of neutrophil granulocytes (a type of white blood cell). ... Thrombotic thrombocytopenic purpura (TTP or Moschcowitz disease) is a rare disorder of the blood coagulation system that in most cases arises from the deficiency or inhibition of the enzyme ADAMTS13, which is responsible for cleaving large multimers of von Willebrand factor. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Aspirin, or acetylsalicylic acid (IPA: ), (acetosal) is a drug in the family of salicylates, often used as an analgesic (to relieve minor aches and pains), antipyretic (to reduce fever), and as an anti-inflammatory. ...

References

1. ^ Preliminary Injunction Against Apotex Upheld on Appeal - Press Release. Retrieved on 2007-09-05.
2. ^ U.S. judge upholds Bristol, Sanofi patent on Plavix. Retrieved on 2007-09-05.
3. ^ IMS HEALTH. Retrieved on 2007-09-05.
4. ^ ^{a b} Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
5. ^ Chan FK, Ching JY, Hung LC, et al (2005). "Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding". N. Engl. J. Med. 352 (3): 238-44. DOI:10.1056/NEJMoa042087. PMID 15659723. 

Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 248th day of the year (249th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 248th day of the year (249th in leap years) in the Gregorian calendar. ... Year 2007 (MMVII) is the current year, a common year starting on Monday of the Gregorian calendar and the AD/CE era. ... is the 248th day of the year (249th in leap years) in the Gregorian calendar. ... The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly general practitioners and pharmacists) in Australia. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• 3418 drug label/data at Daily Med from U.S. National Library of Medicine, National Institutes of Health.
• Plavix : Information for the General Public
• Plavix, Aspirin and Stents : Patients' Forum : Angioplasty.Org