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Mechanism of Action
Ticlopidine¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ 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.
Pharmacology
Ticlopidine¿¡ ´ëÇÑ Pharmacology Á¤º¸ Ticlopidine is a platelet aggregation inhibitor structurally and pharmacologically similar to clopidogrel. When taken orally, ticlopidine causes a time- and dose-dependent inhibition of both platelet aggregation and release of platelet granule constituents, as well as a prolongation of bleeding time. The intact drug has no significant in vitro activity at the concentrations attained in vivo; and, although analysis of urine and plasma indicates at least 20 metabolites, no metabolite which accounts for the activity of ticlopidine has been isolated.
Metabolism
Ticlopidine¿¡ ´ëÇÑ Metabolism Á¤º¸ # Phase_1_Metabolizing_Enzyme:Cytochrome P450 3A4 (CYP3A4)Cytochrome P450 2C19 (CYP2C19)Cytochrome P450 2B6 (CYP2B6)
Protein Binding
Ticlopidine¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ 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. At concentrations attained with the recommended dose, only 15% or less ticlopidine in plasma is bound to this protein.
Half-life
Ticlopidine¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 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.
Absorption
Ticlopidine¿¡ ´ëÇÑ Absorption Á¤º¸ Absorption is greater than 80%. Food increases absorption.
Pharmacokinetics
Ticlopidine HClÀÇ ¾à¹°µ¿·ÂÇÐÀÚ·á
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Biotransformation
Ticlopidine¿¡ ´ëÇÑ Biotransformation Á¤º¸ Metabolized extensively by the liver; only trace amounts of intact drug are detected in the urine. At least 20 metabolites have been identified. It has been proposed that 1 or more active metabolites may account for ticlopidine's activity, because ticlopidine itself is an extremely weak platelet aggregation inhibitor in vitro at the concentrations achieved in vivo. However, no active metabolite has been identified.
Toxicity
Ticlopidine¿¡ ´ëÇÑ Toxicity Á¤º¸ 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.
Drug Interactions
Ticlopidine¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Not Available
CYP450 Drug Interaction
[CYP450 TableÁ÷Á¢Á¶È¸] Ticlopidine¿¡ ´ëÇÑ P450 table SUBSTRATES
CYP 1A2
clozapine
cyclobenzaprine
imipramine
mexiletine
naproxen
riluzole
tacrine
theophylline
INHIBITORS
CYP 1A2
cimetidine
fluoroquinolones
fluvoxamine
**ticlopidine**
INDUCERS
CYP 1A2
tobacco
SUBSTRATES
CYP 2C19
Proton Pump Inhibitors:
omeprazole
lansoprazole
pantoprazole
rabeprazole
Anti-epileptics:
diazepam
phenytoin
phenobarbitone
amitriptyline
clomipramine
clopidogrel
cyclophosphamide
progesterone
INHIBITORS
CYP 2C19
fluoxetine
fluvoxamine
ketoconazole
lansoprazole
omeprazole
**ticlopidine**
INDUCERS
CYP 2C19
N/A
Food Interaction
Ticlopidine¿¡ ´ëÇÑ Food Interaction Á¤º¸ Not Available
Drug Target
[Drug Target]
Description
Ticlopidine¿¡ ´ëÇÑ Description Á¤º¸ Ticlopidine is an effective inhibitor of platelet aggregation. The drug has been found to significantly reduce infarction size in acute myocardial infarcts and is an effective antithrombotic agent in arteriovenous fistulas, aorto-coronary bypass grafts, ischemic heart disease, venous thrombosis, and arteriosclerosis. [PubChem]
Drug Category
Ticlopidine¿¡ ´ëÇÑ Drug_Category Á¤º¸ Fibrinolytic AgentsPlatelet Aggregation Inhibitors
Smiles String Canonical
Ticlopidine¿¡ ´ëÇÑ Smiles_String_canonical Á¤º¸ ClC1=CC=CC=C1CN1CCC2=C(C1)C=CS2
Smiles String Isomeric
Ticlopidine¿¡ ´ëÇÑ Smiles_String_isomeric Á¤º¸ ClC1=CC=CC=C1CN1CCC2=C(C1)C=CS2
InChI Identifier
Ticlopidine¿¡ ´ëÇÑ InChI_Identifier Á¤º¸ InChI=1/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
Chemical IUPAC Name
Ticlopidine¿¡ ´ëÇÑ Chemical_IUPAC_Name Á¤º¸ 5-[(2-chlorophenyl)methyl]-6,7-dihydro-4H-thieno[3,2-c]pyridine
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The database contains the following fields:
The generic name of each chemical
For module A10 (liver enzyme composite module):
Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the number of active and marginally active scores for each compound at the five individual endpoints (see research article for full description of method)
Number of endpoints at which each compound is marginally active (M)
Number of endpoints at which each compound is active (A)
For modules A11 to A15 (alkaline phosphatase increased, SGOT increased, SGPT increased, LDH increased, and GGT increased, respectively):
Overall activity category for each compound (A for active, M for marginally active, or I for inactive) based on the RI and ADR values (see the research article for full description of method)
Number of ADR reports for each compound, given as <4 or ¡Ã4
Reporting Index value for each compound, except where no shipping units were available (NSU)
Group 1 comprises of compounds for which ADR data were available for the first five years of marketing, so when no ADR reports were listed during this period the compounds were evaluated as inactive. Group 2 comprises of compounds for which a 'steady state' period of ADR data were available (1992-1996). In cases where no ADR reports were filed during this period, the compounds were scored as 'NA' (data not available) since they may have had one or more ADR reports during their first five years of marketing which should not be negated by a lack of ADR reports during the steady-state period.
TICLOPIDINE [GGT Increase] [Composite Activity] (Score) I (Marginal) 0 (Active) 0 [Alkaline Phosphatase Increase] (Activity Score) I (Number of Rpts) <4 (Index value) 0 [SGOT Increase] (Activity Score) I (Number of Rpts) <4 (Index value) 0 [SGPT Increase] (Activity Score) I (Number of Rpts) <4 (Index value) 0 [LDH Increase] (Activity Score) I (Number of Rpts) <4 (Index value) 0 [GGT Increase] (Activity Score) I (Number of Rpts) <4 (Index value) 0
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