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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. 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 They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Chlorine (ˈklɔriːn from the Greek word 'χλωρóς' ( khlôros, meaning 'pale green' is the Chemical element with Atomic number 17 and Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Sulfur or sulphur (ˈsʌlfɚ see spelling below) is the Chemical element that has the Atomic number 16 The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 82 g/mol
SMILES eMolecules & PubChem
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)
Legal status

Prescription Only (S4)(AU) POM(UK) ℞-only(US)
Routes Oral
A box of Plavix
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. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency 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 a vital organ in the human body and is present in Vertebrates and some other animals The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles 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 For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The Standard for the Uniform Scheduling of Drugs and Poisons, abbreviated SUSDP, is a document used in the regulation of drugs and poisons in Australia. For a topic outline on this subject see List of basic Australia topics. A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route An antiplatelet drug is a member of a class of pharmaceuticals that decreases Platelet aggregation and inhibits Thrombus formation Coronary artery disease (CAD (or atherosclerotic Heart disease) is the end result of the accumulation of atheromatous plaques within the walls Peripheral vascular disease (PVD also known as peripheral artery disease (PAD or peripheral artery occlusive disease (PAOD is a collator for all Diseases Cerebrovascular disease is a group of brain dysfunctions related to disease of blood vessels supplying the brain It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix, and by Sun Pharmaceuticals under the trade name Clopilet. Bristol-Myers Squibb ( colloquially referred to as BMS, is a Pharmaceutical Corporation, formed by a 1989 merger between pharmaceutical companies Sanofi-Aventis () headquartered in Paris, France, is a multinational pharmaceutical company A trade name, also known as a trading name or a business name, is the name which a Business trades under for commercial purposes although its registered } Sun Pharmaceuticals (or Sun Pharmaceuticals Industries Limited ( Bombay Stock Exchange symbolSUN is an international Pharmaceutical company based in Mumbai A trade name, also known as a trading name or a business name, is the name which a Business trades under for commercial purposes although its registered It works by blocking a receptor called P2Y12. In the field of Molecular biology, the P2Y12 Protein is found on the surface of Blood Platelet cells and is an important regulator Adverse effects include hemorrhage. Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from

Contents

Pharmacology

The mechanism of action of clopidogrel is an irreversible blockade of the adenosine diphosphate (ADP) receptor on platelet cell membranes. Adenosine diphosphate, abbreviated ADP, is a Nucleotide. It is an Ester of Pyrophosphoric acid with the Nucleoside Adenosine Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved This receptor is named P2Y12 and is important in platelet aggregation, the cross-linking of platelets by fibrin. In the field of Molecular biology, the P2Y12 Protein is found on the surface of Blood Platelet cells and is an important regulator Fibrin (also called Factor Ia) is a Protein involved in the clotting of blood The blockade of this receptor inhibits platelet aggregation by blocking activation of the glycoprotein IIb/IIIa pathway. 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:[1]

It is also used, along with aspirin, for the prevention of thromboembolism after placement of intracoronary stent. In Medicine, ischemia ( Greek ισχαιμία, isch- is restriction hema or haema is Blood) is a restriction Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply [1]

International guidelines granted the highest grade of recommendation for NSTE-ACS, PCI and stent, for Clopidogrel in addition to Aspirin. Consensus-based therapeutic guidelines recommend also the use of clopidogrel, instead of 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. Aspirin, or acetylsalicylic acid (ASA (əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd is a Salicylate drug, often used as an Analgesic to relieve 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. Proton pump inhibitors (or "PPI"s are a group of drugs whose main action is pronounced and long-lasting reduction of Gastric acid production [2]

Dosage forms

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

Pharmacokinetics and Metabolism

The active metabolite of clopidogrel
The active metabolite of clopidogrel [3]

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 a pro-drug which requires metabolism by the liver for its activation. The active metabolite has an elimination half-life of about 8 hours and acts by forming a disulfide bridge with the platelet ADP receptor.

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.

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.

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. Carboxylic acids are Organic acids characterized by the presence of a Carboxyl group, which has the formula -C(=OOH usually written -COOH or -CO2H In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed.

Adverse effects

Serious adverse drug reactions associated with clopidogrel therapy include:

Marketing

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. Country to "Dominion of Canada" or "Canadian Federation" or anything else please read the Talk Page Bristol-Myers Squibb ( colloquially referred to as BMS, is a Pharmaceutical Corporation, formed by a 1989 merger between pharmaceutical companies [4] The court ruled that Bristol-Myers Squibb's patent was valid and has patent protection until November 2011. [5] 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. [6] Generic clopidogrel is also produced by several pharmaceutical companies in India at significantly lower retail prices, up to 1/30th of the price.

Research into migraine treatment

Dr. John Chambers, a cardiologist in London, recently reported that the use of clopidogrel in patients with a history of migraines worked "spectacularly well" in some cases. A wider study is planned and has received considerable support from within the British medical community. [7]

References

  1. ^ a b Rossi S, editor. Australian Medicines Handbook 2006. The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly General practitioners Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
  2. ^ 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. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15659723.  
  3. ^ J. M. Pereillo, M. Maftouh, A. Andrieu, M. F. Uzabiaga, O. Fedeli, P. Savi, M. Pascal, J. M. Herbert, J. P. Maffrand, C. Picard (2002). "Structure and stereochemistry of the active metabolite of clopidogrel". Drug Metab. Dispos. 30 (11): 1288-1295. PMID 12386137.  
  4. ^ Preliminary Injunction Against Apotex Upheld on Appeal - Press Release. Retrieved on 2007-09-05. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1590 - Alexander Farnese 's army forces Henry IV of France to raise the siege of Paris.
  5. ^ U.S. judge upholds Bristol, Sanofi patent on Plavix. Retrieved on 2007-09-05. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1590 - Alexander Farnese 's army forces Henry IV of France to raise the siege of Paris.
  6. ^ IMS HEALTH. Retrieved on 2007-09-05. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1590 - Alexander Farnese 's army forces Henry IV of France to raise the siege of Paris.
  7. ^ Jeremy, Laurance. "Drug promises end to migraine misery", Independent Online Edition, Independent News and Media Limited, 2007-12-26. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1481 - Battle of Westbrook - Holland defeats troops of Utrecht. Retrieved on 2007-12-26. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1481 - Battle of Westbrook - Holland defeats troops of Utrecht.  

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