药品详细

Ticlopidine(噻氯匹定)

基本信息
剂型规格
适应症
药理
临床
理化性质
相互作用
文档
专利
Pathway
文献
序列

化学结构式图

中文名

噻氯匹定

英文名

Ticlopidine

分子式

C₁₄H₁₄ClNS

化学名

5-[(2-chlorophenyl)methyl]-4H,5H,6H,7H-thieno[3,2-c]pyridine

分子量

Average: 263.786
Monoisotopic: 263.05354785

CAS号

55142-85-3

ATC分类

B01A 抗血栓药

药物类型

small molecule

阶段

approved

商品名

同义名

基本介绍

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.

生产厂家

Actavis elizabeth llc
Apotex inc
Caraco pharmaceutical laboratories ltd
Genpharm inc
Mylan pharmaceuticals inc
Roche palo alto llc
Sandoz inc
Teva pharmaceuticals usa inc
Watson laboratories inc

封装厂家

Apotex Inc.
AQ Pharmaceuticals Inc.
Caraco Pharmaceutical Labs
Eon Labs
F Hoffmann-La Roche Ltd.
Major Pharmaceuticals
Mylan
Physicians Total Care Inc.
Resource Optimization and Innovation LLC
Sandhills Packaging Inc.
Teva Pharmaceutical Industries Ltd.
Torpharm Inc.

参考

Synthesis Reference	Not Available
General Reference	FDA label.

剂型

规格

化合物类型

Type	small molecule

Classes

Thienopyridines

Substructures

Thienopyridines
Benzene and Derivatives
Aryl Halides
Halobenzenes
Aliphatic and Aryl Amines
Heterocyclic compounds
Aromatic compounds
Thiophenes

适应症

药理

Indication

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.

Pharmacodynamics

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.

Mechanism of action

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.

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.

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

Substrate	Enzymes	Product
Ticlopidine	Cytochrome P450 2C19	Hydroxyticlopidine	Details
Ticlopidine	Myeloperoxidase	2-Chloroticlopidine	Details
Ticlopidine	Cytochrome P450 3A4 Cytochrome P450 2C19	2-Oxoticlopidine	Details
Ticlopidine	Myeloperoxidase Cytochrome P450 3A4 Cytochrome P450 2C19	Thienodihydropyridinium	Details
Ticlopidine	Cytochrome P450 2C19 Cytochrome P450 2D6	Ticlopidine S-oxide	Details
Ticlopidine	Myeloperoxidase	Dehydrogenated ticlopidine	Details
Ticlopidine	Myeloperoxidase	Ticlopidine N-oxide	Details
Ticlopidine	Cytochrome P450 2C19	di-Hydroxyticlopidine	Details
Ticlopidine		7-Hydroxyticlopidine	Details

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.

Toxicity

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.

Affected organisms

Humans and other mammals

Pathways

Pathway	Name	SMPDB ID
	Ticlopidine Pathway	SMP00261

理化性质

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	approx. 1 189°C	From Remington: The Science and Practice of Pharmacy
water solubility	Freely soluble	From Remington: The Science and Practice of Pharmacy
logP	2.9	Not Available

Predicted Properties

Property	Value	Source
water solubility	2.19e-02 g/l	ALOGPS
logP	4.25	ALOGPS
logP	4.2	ChemAxon
logS	-4.1	ALOGPS
pKa (strongest basic)	7.31	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	1	ChemAxon
hydrogen donor count	0	ChemAxon
polar surface area	3.24	ChemAxon
rotatable bond count	2	ChemAxon
refractivity	74.33	ChemAxon
polarizability	27.99	ChemAxon

药物相互作用

Drug	Interaction
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.

食物相互作用

High fat meals will increase ticlopidine absorption. As well, food can help ticlopidine-induced stomach upset.

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