Tìm theo
Ticlopidine
Các tên gọi khác (2) :
  • Ticlopidina
  • Ticlopidinum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 55142-85-3
ATC: B01AC05
ĐG : Apotex Inc. , http://www.apotex.com
CTHH: C14H14ClNS
PTK: 263.786
Ticlopidine is an effective inhibitor of platelet aggregation. It is a prodrug that is metabolised to an active form, which blocks the ADP receptor that is involved in GPIIb/IIIa receptor activation leading to platelet aggregation. Ticlopidine is marketed under the brand name Ticlid and is indicated for patients who cannot take aspirin or in whom aspirin has not worked to prevent a thrombotic stroke. The FDA label includes a black-box warning of neutropenia, aplastic anemia, thrombotic thrombocytopenia purpura, and agranulocytosis, so it is necessary to monitor patients' WBC and platelets when they are taking ticlopidine.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H14ClNS
Phân tử khối
263.786
Monoisotopic mass
263.05354785
InChI
InChI=1S/C14H14ClNS/c15-13-4-2-1-3-11(13)9-16-7-5-14-12(10-16)6-8-17-14/h1-4,6,8H,5,7,9-10H2
InChI Key
InChIKey=PHWBOXQYWZNQIN-UHFFFAOYSA-N
IUPAC Name
5-[(2-chlorophenyl)methyl]-4H,5H,6H,7H-thieno[3,2-c]pyridine
Traditional IUPAC Name
ticlopidine
SMILES
ClC1=CC=CC=C1CN1CCC2=C(C1)C=CS2
Độ tan chảy
approx. 1 189°C
Độ hòa tan
Freely soluble
logP
2.9
logS
-4.1
pKa (Strongest Basic)
7.31
PSA
3.24 Å2
Refractivity
74.33 m3·mol-1
Polarizability
27.99 Å3
Rotatable Bond Count
2
H Bond Acceptor Count
1
H Bond Donor Count
0
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Ticlopidine is a prodrug that is metabolised to an as yet undetermined metabolite that acts as a platelet aggregation inhibitor. Inhibition of platelet aggregation causes a prolongation of bleeding time. In its prodrug form, ticlopidine has no significant in vitro activity at the concentrations attained in vivo.
Cơ Chế Tác Dụng : Ticlopidine is an effective inhibitor of platelet aggregation. It is a prodrug that is metabolised to an active form, which blocks the ADP receptor that is involved in GPIIb/IIIa receptor activation leading to platelet aggregation. Ticlopidine is marketed under the brand name Ticlid and is indicated for patients who cannot take aspirin or in whom aspirin has not worked to prevent a thrombotic stroke. The FDA label includes a black-box warning of neutropenia, aplastic anemia, thrombotic thrombocytopenia purpura, and agranulocytosis, so it is necessary to monitor patients' WBC and platelets when they are taking ticlopidine. The active metabolite of ticlopidine 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. 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 ticlopidine.
Dược Động Học :
▧ Absorption :
Absorption is greater than 80%. Food increases absorption by approximately 20%.
▧ Volume of Distribution :
The volume of distribution was not quantified.
▧ Protein binding :
Binds reversibly (98%) to plasma proteins, mainly to serum albumin and lipoproteins. The binding to albumin and lipoproteins is nonsaturable over a wide concentration range. Ticlopidine also binds to alpha-1 acid glycoprotein (about 15% or less).
▧ Metabolism :
Ticlopidine is metabolized extensively by the liver with only trace amounts of intact drug detected. At least 20 metabolites have been identified.
▧ Route of Elimination :
Ticlopidine is eliminated mostly in the urine (60%) and somewhat in the feces (23%).
▧ Half Life :
Half-life following a single 250-mg dose is approximately 7.9 hours in subjects 20 to 43 years of age and 12.6 hours in subjects 65 to 76 years of age. With repeated dosing (250 mg twice a day), half-life is about 4 days in subjects 20 to 43 years of age and about 5 days in subjects 65 to 76 years of age.
▧ Clearance :
Ticlopidine clearance was not quantified, but clearance decreases with age.
Độc Tính : Single oral doses of ticlopidine at 1600 mg/kg and 500 mg/kg were lethal to rats and mice, respectively. Symptoms of acute toxicity were GI hemorrhage, convulsions, hypothermia, dyspnea, loss of equilibrium and abnormal gait. The FDA label includes a black-box warning of neutropenia, aplastic anemia, thrombotic thrombocytopenia purpura, and agranulocytosis, so it is necessary to monitor patients' WBC and platelets when they are taking ticlopidine.
Chỉ Định : Used in patients, who have had a stroke or stroke precursors and who cannot take aspirin or aspirin has not worked, to try to prevent another thrombotic stroke.
Tương Tác Thuốc :
  • Acetylsalicylic acid Increased effect of ticlopidine
  • Alteplase Increased bleeding risk. Monitor for signs of bleeding.
  • ambrisentan Ticlopidine may decrease the metabolism and clearance of Ambrisentan. Consider alternate therapy or monitor for adverse/toxic effects of Ambrisentan if Ticlopidine is initiated, discontinued or dose changed.
  • Aminophylline Ticlopidine increases the effect and toxicity of theophylline
  • Bortezomib Ticlopidine may decrease the metabolism and clearance of Bortezomib. Consider alternate therapy or monitor for adverse/toxic effects of Bortezomib if Ticlopidine is initiated, discontinued or dose changed.
  • Carbamazepine Ticlopidine increases the effect of carbamazepine
  • Carisoprodol Ticlopidine may decrease the metabolism and clearance of Carisoprodol. Consider alternate therapy or monitor for adverse/toxic effects of Carisoprodol if Ticlopidine is initiated, discontinued or dose changed.
  • Cilostazol Ticlopidine may decrease the metabolism and clearance of Cilostazol. Consider alternate therapy or monitor for adverse/toxic effects of Cilostazol if Ticlopidine is initiated, discontinued or dose changed.
  • Cimetidine Cimetidine may increase Ticlopidine levels. Avoid concomitant therapy.
  • Citalopram Ticlopidine may decrease the metabolism and clearance of Citalopram. Consider alternate therapy or monitor for adverse/toxic effects of Citalopram if Ticlopidine is initiated, discontinued or dose changed.
  • Clobazam Ticlopidine may decrease the metabolism and clearance of Clobazam. Consider alternate therapy or monitor for adverse/toxic effects of Clobazam if Ticlopidine is initiated, discontinued or dose changed.
  • Clomipramine Ticlopidine may decrease the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for adverse/toxic effects of Clomipramine if Ticlopidine is initiated, discontinued or dose changed.
  • Cyclosporine Ticlopidine decreases the effect of cyclosporine
  • Diazepam Ticlopidine may decrease the metabolism and clearance of Diazepam. Consider alternate therapy or monitor for adverse/toxic effects of Diazepam if Ticlopidine is initiated, discontinued or dose changed.
  • Digoxin Ticlopidine may decrease Digoxin levels. Monitor for Digoxin levels with Ticlopidine is initiated, discontinued or dose changed.
  • Dyphylline Ticlopidine increases the effect and toxicity of theophylline
  • Escitalopram Ticlopidine may decrease the metabolism and clearance of Escitalopram. Consider alternate therapy or monitor for adverse/toxic effects of Ambrisentan if Escitalopram is initiated, discontinued or dose changed.
  • Ethotoin Ticlopidine increases the effect of hydantoin
  • Fosphenytoin Ticlopidine may decrease the metabolism and clearance of Fosphenytoin. Consider alternate therapy or monitor for adverse/toxic effects of Fosphenytoin if Ticlopidine is initiated, discontinued or dose changed.
  • Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
  • Heparin Increased bleeding risk. Monitor aPTT.
  • Ifosfamide Ticlopidine may decrease the metabolism and clearance of Ifosfamide. Consider alternate therapy or monitor for adverse/toxic effects of Ifosfamide if Ticlopidine is initiated, discontinued or dose changed.
  • Imipramine Ticlopidine may decrease the metabolism and clearance of Imipramine. Consider alternate therapy or monitor for adverse/toxic effects of Imipramine if Ticlopidine is initiated, discontinued or dose changed.
  • Mephenytoin Ticlopidine increases the effect of hydantoin
  • Methsuximide Ticlopidine may decrease the metabolism and clearance of Methsuximide. Consider alternate therapy or monitor for adverse/toxic effects of Methsuximide if Ticlopidine is initiated, discontinued or dose changed.
  • Moclobemide Ticlopidine may decrease the metabolism and clearance of Moclobemide. Consider alternate therapy or monitor for adverse/toxic effects of Moclobemide if Ticlopidine is initiated, discontinued or dose changed.
  • Nilutamide Ticlopidine may decrease the metabolism and clearance of Nilutamide. Consider alternate therapy or monitor for adverse/toxic effects of Nilutamide if Ticlopidine is initiated, discontinued or dose changed.
  • Oxtriphylline Ticlopidine increases the effect and toxicity of theophylline
  • Pentamidine Ticlopidine may decrease the metabolism and clearance of Pentamidine. Consider alternate therapy or monitor for adverse/toxic effects of Pentamidine if Ticlopidine is initiated, discontinued or dose changed.
  • Phenobarbital Ticlopidine may decrease the metabolism and clearance of Phenobarbital. Consider alternate therapy or monitor for adverse/toxic effects of Phenobarbital if Ticlopidine is initiated, discontinued or dose changed.
  • Phenytoin Ticlopidine may decrease the metabolism and clearance of phenytoin. Consider alternate therapy or monitor for adverse/toxic effects of phenytoin if ticlopidine is initiated, discontinued or dose changed.
  • Pimozide Avoid combination with pimozide and other major CYP3A4 substrates due to the potential increase of pimozide concentration.
  • Reteplase Increased bleeding risk. Monitor for signs of bleeding.
  • Sodium bicarbonate Sodium bicarbonate may decrease Ticlopidine levels. Administer agents 1 to 2 hours apart.
  • Streptokinase Increased bleeding risk. Monitor for signs of bleeding.
  • Tamoxifen Ticlopidine may decrease the therapeutic effect of tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Ticlopidine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Ticlopidine is initiated, discontinued, or dose changed.
  • Tenecteplase Increased bleeding risk. Monitor for signs of bleeding.
  • Theophylline Ticlopidine increases the effect and toxicity of theophylline
  • Thioridazine Ticlopidine may decrease the metabolism of thioridazine. Concomitant therapy is contraindicated.
  • Tizanidine Ticlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
  • Tramadol Ticlopidine may decrease the effect of Tramadol by decreasing active metabolite production.
  • Treprostinil The prostacyclin analogue, Treprostinil, increases the risk of bleeding when combined with the antiplatelet agent, Ticlopidine. Monitor for increased bleeding during concomitant thearpy.
  • Trimipramine The strong CYP2C19 inhibitor, ticlopidine, may decrease the metabolism and clearance of trimipramine, a CYP2C19 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of trimipramine if ticlopidine is initiated, discontinued or dose changed.
  • Warfarin Increased bleeding risk. Monitor INR.
Liều Lượng & Cách Dùng : Tablet - Oral - 250MG
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty : ROCHE PALO
    Sản phẩm biệt dược : Ticlid
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00208
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5472
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504438
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07140
ChemSpider
http://www.chemspider.com/Chemical-Structure.5273.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0004-0018-23
PharmGKB
http://www.pharmgkb.org/drug/PA451686
Wikipedia
http://en.wikipedia.org/wiki/Ticlopidine
RxList
http://www.rxlist.com/cgi/generic/ticlop.htm
Drugs.com
http://www.drugs.com/cdi/ticlopidine.html
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