| Drug Name: |
Sulodexide |
| Applications: |
The product 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. |
| Examples of Clinical Use: |
Vascular diseases, diabetic kidney disease and diabetic neuropathy |
| Pharmacodynamics: |
The low molecular weight of the product fractions allows for extensive oral absorption compared to unfractionated heparin. The pharmacological effects 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, the product 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 the product 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. 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. |
| Mechanism of action: |
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). |
| Affected organisms: |
Humans and other mammals |
| Targets: |
Target 1. Heparin cofactor 2; Target 2. Antithrombin-III |
