Tìm theo
Sulodexide
antithrombins, fibrinolytic agents, hypoglycemic agents, anticoagulants, hypolipidemic agents
Thuốc Gốc
Biotech
CAS: 57821-29-1
ATC: B01AB11
PTK: 5000-8000 Da
Sulodexide is a mixture of glycosaminoglycans (GAGs) composed of dermatan sulfate (DS) and fast moving heparin (FMH).
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Phân tử khối
5000-8000 Da
Dược Lực Học : The low molecular weight of both sulodexide fractions allows for extensive oral absorption compared to unfractionated heparin. The pharmacological effects of sulodexide differ substantially from other glycosaminoglycans and are mainly characterized by a prolonged half-life and reduced effect on global coagulation and bleeding parameters. Due to the presence of both glycosaminoglycan fractions, sulodexide potentiates the antiprotease activities of both antithrombin III and heparin cofactor II simultaneously. It is capable of inhibiting both anti-IIa and anti-Xa. It promotes fibrinolytic activity by releasing tissue plasminogen activator and reduces plasminogen activator inhibitor. The drug also blocks platelet adhesion and platelet function induced by cathepsin G and thrombin. Research has also shown that Sulodexide had endothelial protective properties by inducing the overexpression of growth factors important for the protection of organs. It has anti-inflammatory properties via its effect on the release of inflammatory mediators from macrophages. This results in anti-proliferative effects such as the regulation of growth factors like VEGF and FGF. The intravenous administration has also been shown capable of releasing tissue factor pathway inhibitor from the endothelium, which also contributes to the anti-thrombotic effects of Sulodexide. Lastly, this drug is known for its ability to inhibit the secretion of MMPs, particularly MMP-9, from leukocytes in a dose dependent manner, resulting in the restoration of the balance with their tissue inhibitors.
Cơ Chế Tác Dụng : Sulodexide is a mixture of glycosaminoglycans (GAGs) composed of dermatan sulfate (DS) and fast moving heparin (FMH). Thrombin inhibition produced by sulodexide is due to the additive effect of its components, namely, heparin cofactor II (HCII) catalysis by dermatan sulfate and antithrombin-III catalysis by fast moving heparin (FMH).
Dược Động Học :
▧ Absorption :
Sulodexide can be administered via the oral route, IV and IM routes. After oral dosing, the absorption rate being equivalent, the bioavailability is 40-60%. either calculated from the fast-moving heparin fraction or from the dermatan fraction. Bioavailability following IM administration is approximately 90%. After a rapid absorption in the intestine, the dermatan and heparin components start to appear in the plasma. Sulodexide is degraded after ingestion and loses its sulfate groups and both sulfated and unsulfated groups circulate in the blood for up to 24hours. AUC=22.83+/-4.44mg.h/L.
▧ Volume of Distribution :
Cmax=516+/-77.54ng/mL, Tmax=1.33+/-0.58h, Vd=71.24+/-14.06L (b phase). Sulodexide reaches high concentrations in the plasma and is widely distributed in the endothelial layer. Binding to endothelial cell receptors in arteries and veins contributes to its rapid distribution profile.
▧ Metabolism :
It is mainly metabolized in the liver.
▧ Route of Elimination :
Sulodexide is eliminated via the renal, fecal and bile routes. The main clearance occurs renally and accounts for elimination of 55+2.9% of the drug over 96 hours. The fecal and bile routes remove the rest of the drug over 48 hours, which accounts for 23.5+/-2.5% for both routes.
▧ Half Life :
The elimination half-life was 11.7 +/- 2.0 h after intravenous administration, 18.7 +/- 4.1 h after 50 mg per os, and 25.8 +/- 1.9 h after 100 mg per os.
▧ Clearance :
2.70+/-0.58L/h
Độc Tính : Sulodexide seems to be well tolerated. Most adverse effects reported are related to the GI system and seem to be transient in nature. Among others adverse reactions are diarrhea, epigastralgia, dyspepsia, heartburn and dizziness. Allergic reactions, such as skin rash, have also been reported but are very rare.
Chỉ Định : Sulodexide has been used clinically for the prophylaxis and treatment of vascular diseases with increased risk of thrombosis, including intermittent claudication, peripheral arterial occlusive disease and post-myocardial infarc-tion. Also investigated in the treatment of diabetic kidney disease and diabetic neuropathy. New anti-inflammatory properties have also extended its use in venous disease.
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Sulonex
  • Công ty :
    Sản phẩm biệt dược : Vessel
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB06271
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08547
PharmGKB
http://www.pharmgkb.org/drug/PA164746343
Wikipedia
http://en.wikipedia.org/wiki/Sulodexide
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