Tìm theo
Clopidogrel
Các tên gọi khác (2) :
  • (+)-Clopidogrel
  • Clopidogrelum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 113665-84-2
ATC: B01AC04
ĐG : Advanced Pharmaceutical Services Inc.
CTHH: C16H16ClNO2S
PTK: 321.822
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C16H16ClNO2S
Phân tử khối
321.822
Monoisotopic mass
321.059027158
InChI
InChI=1S/C16H16ClNO2S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14/h2-5,7,9,15H,6,8,10H2,1H3/t15-/m0/s1
InChI Key
InChIKey=GKTWGGQPFAXNFI-HNNXBMFYSA-N
IUPAC Name
methyl (2S)-2-(2-chlorophenyl)-2-{4H,5H,6H,7H-thieno[3,2-c]pyridin-5-yl}acetate
Traditional IUPAC Name
clopidogrel
SMILES
[H][C@@](N1CCC2=C(C1)C=CS2)(C(=O)OC)C1=CC=CC=C1Cl
Độ tan chảy
158 °C
Độ hòa tan
50.78 mg/L
logP
2.5
logS
-4.4
pKa (Strongest Basic)
5.14
PSA
29.54 Å2
Refractivity
84.93 m3·mol-1
Polarizability
33.19 Å3
Rotatable Bond Count
4
H Bond Acceptor Count
2
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ Absorption :
Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites. Bioavailability has not been found to be affected by food.
▧ 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.
▧ 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.
Độc Tính : 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.
Chỉ Định : 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.
Tương Tác Thuốc :
  • 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.
Liều Lượng & Cách Dùng : Tablet, film coated - Oral - 300 mg (pink, oblong)
Tablet, film coated - Oral - 75 mg (pink, biconvex)
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Plavix 75 mg tablet
    Giá bán buôn : USD >9.23
    Đơn vị tính : tablet
  • Biệt dược thương mại : Plavix 300 mg tablet
    Giá bán buôn : USD >24.86
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Sanofi
    Sản phẩm biệt dược : Plavix
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00758
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00769
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/63653-1171-6
PharmGKB
http://www.pharmgkb.org/drug/PA449053
Wikipedia
http://en.wikipedia.org/wiki/Clopidogrel
RxList
http://www.rxlist.com/cgi/generic/clopidog.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/pla1338.shtml
Drugs.com
http://www.drugs.com/cdi/clopidogrel.html
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