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药品详细

Clopidogrel(氯吡格雷)

化学结构式图
中文名
氯吡格雷
英文名
Clopidogrel
分子式
C16H16ClNO2S
化学名
methyl (2S)-2-(2-chlorophenyl)-2-{4H,5H,6H,7H-thieno[3,2-c]pyridin-5-yl}acetate
分子量
Average: 321.822
Monoisotopic: 321.059027158
CAS号
113665-84-2
ATC分类
B01A 抗血栓药
药物类型
small molecule
阶段
approved, nutraceutical
商品名
同义名
基本介绍

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. The drug is an irreversible inhibitor of the P2Y12 adenosine diphosphate receptor found on the membranes of platelet cells. Clopidogrel use is associated with several serious adverse drug reactions such as severe neutropenia, various forms of hemorrhage, and cardiovascular edema.

生产厂家
  • Dr reddys laboratories inc
  • Sanofi aventis us llc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Chan FK, Ching JY, Hung LC, Wong VW, Leung VK, Kung NN, Hui AJ, Wu JC, Leung WK, Lee VW, Lee KK, Lee YT, Lau JY, To KF, Chan HL, Chung SC, Sung JJ: Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med. 2005 Jan 20;352(3):238-44. Pubmed
  2. Perry CG, Shuldiner AR: Pharmacogenomics of anti-platelet therapy: how much evidence is enough for clinical implementation? J Hum Genet. 2013 May 23. doi: 10.1038/jhg.2013.41. Pubmed
  3. Furlong MT, Savant I, Yuan M, Scott L, Mylott W, Mariannino T, Kadiyala P, Roongta V, Arnold ME: A validated HPLC-MS/MS assay for quantifying unstable pharmacologically active metabolites of clopidogrel in human plasma: application to a clinical pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 2013 May 1;926:36-41. doi: 10.1016/j.jchromb.2013.02.031. Epub 2013 Mar 1. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes Not Available
Substructures Not Available
适应症
药理
Indication For the reduction of atherosclerotic events (myocardial infarction, stroke, and vascular death) in patients with atherosclerosis documented by recent stroke, recent myocardial infarction, or established peripheral arterial disease.
Pharmacodynamics Since clopidogrel is a prodrug, it must be metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. This active metabolite selectively inhibits adenosine diphosphate (ADP) binding to its platelet P2Y12 receptor and subsequently the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.
Mechanism of action The active metabolite of clopidogrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. It is proposed that the inhibition involves a defect in the mobilization from the storage sites of the platelet granules to the outer membrane. he drug specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor, which is important in aggregation of platelets and cross-linking by the protein fibrin. No direct interference occurs with the GPIIb/IIIa receptor. As the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, its impaired activation prevents fibrinogen binding to platelets and inhibits platelet aggregation. By blocking the amplification of platelet activation by released ADP, platelet aggregation induced by agonists other than ADP is also inhibited by the active metabolite of clopidogrel.
Absorption Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites. Bioavailability has not been found to be affected by food.
Volume of distribution Not Available
Protein binding 98%
Metabolism
Hepatic, extensive and rapid, by hydrolysis to the main circulating metabolite, a carboxylic acid derivative, which accounts for approximately 85% of the circulating drug-related compounds. A glucuronic acid derivative of the carboxylic acid derivative has also been found in plasma and urine. Neither the parent compound nor the carboxylic acid derivative has a platelet inhibiting effect.

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Clopidogrel
2-Oxoclopidogrel Details
Route of elimination Following an oral dose of 14C-labeled clopidogrel in humans, approximately 50% of total radioactivity was excreted in urine and approximately 46% in feces over the 5 days post-dosing.
Half life Carboxylic acid derivative: 8 hours (after single and multiple doses). Covalent binding to platelets has accounted for 2% of radiolabeled clopidogrel with a half-life of 11 days.
Clearance Not Available
Toxicity A single dose of clopidogrel at 1500 or 2000 mg/kg was lethal to mice and rats, with 3000 mg/kg lethal to baboons. Symptoms included vomiting, breathing difficulty, hemorrhage, and prostration.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00260 Clopidogrel Pathway SMP00260
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 158 °C Not Available
water solubility 50.78 mg/L Not Available
logP 2.5 Not Available
Predicted Properties
Property Value Source
water solubility 1.18e-02 g/l ALOGPS
logP 3.84 ALOGPS
logP 4.03 ChemAxon
logS -4.4 ALOGPS
pKa (strongest basic) 5.14 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 29.54 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 84.93 ChemAxon
polarizability 33.19 ChemAxon
药物相互作用
Drug Interaction
Bortezomib Moderate CYP2C19 Inhibitors like bortezomib may decrease serum concentrations of the active metabolite(s) of Clopidogrel. Avoid concurrent use of moderate CYP2C19 inhibitors with clopidogrel whenever possible. If such a combination must be used, monitor closely for evidence of reduced clinical response to clopidogrel.
Drotrecogin alfa Antiplatelet agents such as clopidogrel may enhance the adverse/toxic effect of Drotrecogin Alfa. Bleeding may occur. Increase monitoring for signs/symptoms of bleeding during concomitant therapy. If possible, avoid use of drotrecogin within 7 days of use of any IIb/IIIa antagonists, higher dose aspirin (more than 650 mg/day), or use of other antiplatelet agents.
Esomeprazole Esomeprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Due to the possible risk for impaired clopidogrel effectiveness with this combination, clinicians should carefully consider the need for concurrent esomeprazole therapy in patients receiving clopidogrel. Monitor response to clopidogrel closely when using clopidogrel with esomeprazole. Whether there are differences among individual proton pump inhibitors is unclear. Other acid-lowering therapies (e.g., H2-receptor antagonists, antacids, etc.) do not appear to share this interaction with clopidogrel.
Etravirine Clopidogrel, when used concomitantly with etravirine (a CYP2C19 inhibitor), may experience a decrease in the serum concentrations of it's active metabolites. Caution and close monitoring for decreased efficacy of clopidogrel is recommended.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Lansoprazole Lansoprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Due to the possible risk for impaired clopidogrel effectiveness with this combination, clinicians should carefully consider the need for concurrent lansoprazole therapy in patients receiving clopidogrel. Monitor response to clopidogrel closely when using clopidogrel with lansoprazole. Whether there are differences among individual proton pump inhibitors is unclear. Other acid-lowering therapies (e.g., H2-receptor antagonists, antacids, etc.) do not appear to share this interaction with clopidogrel.
Omeprazole Omeprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Clopidogrel prescribing information recommends avoiding concurrent use with omeprazole, due to the possibility that combined use may result in decreased clopidogrel effectiveness.
Pantoprazole Pantoprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Due to the possible risk for impaired clopidogrel effectiveness with this combination, clinicians should carefully consider the need for concurrent pantoprazole therapy in patients receiving clopidogrel. Monitor response to clopidogrel closely when using clopidogrel with pantoprazole. Whether there are differences among individual proton pump inhibitors is unclear. Other acid-lowering therapies (e.g., H2-receptor antagonists, antacids, etc.) do not appear to share this interaction with clopidogrel.
Rabeprazole Rabeprazole may decrease serum concentrations of the active metabolite(s) of clopidogrel. Due to the possible risk for impaired clopidogrel effectiveness with this combination, clinicians should carefully consider the need for concurrent rabeprazole therapy in patients receiving clopidogrel. Monitor response to clopidogrel closely when using clopidogrel with rabeprazole. Whether there are differences among individual proton pump inhibitors is unclear. Other acid-lowering therapies (e.g., H2-receptor antagonists, antacids, etc.) do not appear to share this interaction with clopidogrel.
Rivaroxaban Antiplatelet agents such as clopidogrel may enhance the anticoagulant effect of rivaroxaban. Avoid concurrent use of clopidogrel with rivaroxaban unless the anticipated benefits outweigh the risks of bleeding. Canadian rivaroxaban labeling recommends avoiding concurrent use with any antiplatelet agent, while the U.S. rivaroxaban labeling recommends caution and increased monitoring if used with any other antiplatelet agent. Any combined use should only be undertaken with increased monitoring for evidence of bleeding.
Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Clopidogrel. Monitor for increased bleeding during concomitant thearpy.
Warfarin Increased bleed risk may occur as a result of additive anticoagulant effects. Increase monitoring for signs and symptoms of bleeding during concomitant therapy.
食物相互作用
Not Available

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