Tìm theo
Prasugrel
Các tên gọi khác (3) :
  • Effient
  • Prasugrel
  • SID124899264
platelet aggregation inhibitors
Thuốc Gốc
Small Molecule
CAS: 150322-43-3
ATC: B01AC22
CTHH: C20H20FNO3S
PTK: 373.441
Prasugrel, a thienopyridine derivative, is a platelet activation and aggregation inhibitor structurally and pharmacologically related to clopidogrel and ticlopidine. Similar to clopidogrel, prasugrel is a prodrug that requires enzymatic transformation in the liver to its active metabolite, R-138727. R-138727 irreversibly binds to P2Y12 type ADP receptors on platelets thus preventing activation of the GPIIb/IIIa receptor complex. As a result, inhibition of ADP-mediated platelet activation and aggregation occurs. Prasugrel was developed by Daiichi Sankyo Co. and is currently marketed in the United States and Canada in cooperation with Eli Lilly and Company for acute coronary syndromes planned for percutaneous coronary intervention (PCI). FDA approved in 2009.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C20H20FNO3S
Phân tử khối
373.441
Monoisotopic mass
373.114792406
InChI
InChI=1S/C20H20FNO3S/c1-12(23)25-18-10-14-11-22(9-8-17(14)26-18)19(20(24)13-6-7-13)15-4-2-3-5-16(15)21/h2-5,10,13,19H,6-9,11H2,1H3
InChI Key
InChIKey=DTGLZDAWLRGWQN-UHFFFAOYSA-N
IUPAC Name
5-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4H,5H,6H,7H-thieno[3,2-c]pyridin-2-yl acetate
Traditional IUPAC Name
prasugrel
SMILES
CC(=O)OC1=CC2=C(CCN(C2)C(C(=O)C2CC2)C2=CC=CC=C2F)S1
Độ hòa tan
2.37e-03 g/l
logP
3.536
logS
-5.2
pKa (strongest acidic)
14.25
pKa (Strongest Basic)
5.48
PSA
46.61 Å2
Refractivity
96.81 m3·mol-1
Polarizability
37.7 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
3
H Bond Donor Count
0
Physiological Charge
0
Number of Rings
4
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Prasugrel is a member of the thienopyridine class of ADP receptor inhibitors, like ticlopidine (trade name Ticlid) and clopidogrel (trade name Plavix). These agents reduce the aggregation ("clumping") of platelets by irreversibly binding to P2Y12 receptors. Compared to clopidogrel, prasugrel inhibits adenosine diphosphate–induced platelet aggregation more rapidly, more consistently, and to a greater extent than do standard and higher doses of clopidogrel in healthy volunteers and in patients with coronary artery disease, including those undergoing PCI. The increased potency of prasugrel appears to be due to more efficient conversion to its active metabolite. However, it carries a higher risk of bleed compared to clopidogrel, which may be a result of its higher potency. Prasugrel produces inhibition of platelet aggregation to 20 μM or 5 μM ADP, as measured by light transmission aggregometry.
Cơ Chế Tác Dụng : Prasugrel, a thienopyridine derivative, is a platelet activation and aggregation inhibitor structurally and pharmacologically related to clopidogrel and ticlopidine. Similar to clopidogrel, prasugrel is a prodrug that requires enzymatic transformation in the liver to its active metabolite, R-138727. R-138727 irreversibly binds to P2Y12 type ADP receptors on platelets thus preventing activation of the GPIIb/IIIa receptor complex. As a result, inhibition of ADP-mediated platelet activation and aggregation occurs. Prasugrel was developed by Daiichi Sankyo Co. and is currently marketed in the United States and Canada in cooperation with Eli Lilly and Company for acute coronary syndromes planned for percutaneous coronary intervention (PCI). FDA approved in 2009. Prasugrel is an thienopyridine and a prodrug which inhibits ADP receptors by irreversibly acting on the P2Y12 receptor on platelets. The active metabolite of prasugrel prevents binding of adenosine diphosphate (ADP) to its platelet receptor, impairing the ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Prasugrel is proposed to have a similar mechanism of action to clopidogrel.
Dược Động Học :
▧ Absorption :
79% or greater of the dose is absorbed after oral administration. Absorption and metabolism occur rapidly and peak plasma concentrations (Cmax) are reached approximately 30 minutes following oral administration. Administration with a high fat, high calorie meal did not affect the AUC of the active metabolite in healthy individuals, but the Cmax was decreased by ~49% and the Tmax was increased to 0.5 to 1.5 hours. Prasugrel may be administered with or without food.
▧ Volume of Distribution :
44-68L
▧ Protein binding :
Approximately 98% of the active metabolite was bound to human serum albumin in a 4% buffered solution. The major inactive metabolites are also highly bound to human plasma proteins.
▧ Metabolism :
Prasugrel is not detected in plasma following oral administration. It is rapidly hydrolyzed in the intestine to thiolactone by human carboxylesterase (hCE) 2. This intermediate is further metabolized to its active metabolite, R-138727, in a single step by cytochrome P450 enzymes in the liver (primarily CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19). The active metabolite is further metabolized by S-methylation or cysteine conjugation to two inactive metabolites. Unlike clopidogrel, transformation of prasugrel to its active metabolite does not appear to be affected by cytochrome P450 polymorphisms.
▧ Route of Elimination :
Approximately 68% of the orally administered dose is excreted in urine and 27% in the feces, as inactive metabolites. The active metabolite is not expected to be removed by dialysis.
▧ Half Life :
The active metabolite has an elimination half-life of about 7.4 hours (range 2-15 hours).
▧ Clearance :
Apparent clearance = 112 - 166 L/hr
Độc Tính : LD50 (rat) 1,000 - 2,000 mg/kg; LD50 (rabbit) > 1,000 mg/kg
Chỉ Định : Indicated in combination with acetylsalicylic acid (ASA) to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI). May be used in patients with unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), ST-elevation myocardial infarction (STEMI) who are to be managed with PCI. Prasugrel is not recommended in patients 75 years of age or greater, those that weigh<60kg, and patients with a history of stroke or transient ischemic attack due to increased risk of fatal and intracranial bleeding.
Tương Tác Thuốc :
  • Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
  • Ibuprofen Coadministration with NSAIDS used chronically may increase the risk of bleeding.
  • Ketoconazole Ketoconazole is a potent inhibitor of CYP3A4 which decreases the Cmax of prasugrel due to a reduction of prasugrel bioactivation. However, there was no reduction of inhibition of platelet aggregation.
  • Lansoprazole Lansoprazole is a CYP2C19 substrate which decreases AUC and Cmax of prasugrel. Despite these decreases, there was no significant reduction of inhibition of platelet aggregation.
  • Ritonavir Ritonavir is a inhibitor of CYP3A4, thus blocking the bioactivation of prasugrel. As a result, a reduction in prasugrel efficiency may be observed in patients.
  • Warfarin Coadministration with warfarin may increase the risk of bleeding.
Liều Lượng & Cách Dùng : Tablet - Oral - 5 mg, 10 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06209
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=6918456
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=99443238
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D05597
ChemSpider
http://www.chemspider.com/Chemical-Structure.5293653.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/54868-6238-0
PharmGKB
http://www.pharmgkb.org/drug/PA154410481
Wikipedia
http://en.wikipedia.org/wiki/Prasugrel
RxList
http://www.rxlist.com/effient-drug.htm
PDRhealth
http://www.pdrhealth.com/drugs/effient
Drugs.com
http://www.drugs.com/cdi/prasugrel.html
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