Pharmacological actions of sulodexide.
This report summarizes the results of some of the studies that have evaluated the pharmacokinetic, pharmacodynamic, anticoagulant, and antithrombotic properties of Sulodexide, which consists of a mixture of electrophoretically fast moving heparin (80% of the mass) and dermatan sulfate (the balance), with an average product (Mr) <8000. The low molecular weight (Mr) of the constituents of Sulodexide would predict that the product has the high bioavailability associated with low-Mr heparin and low-Mr dermatan sulfate. Given orally, subcutaneously, or by intravenous injection, Sulodexide exhibits antithrombotic and profibrinolytic properties in several animal models of venous and arterial thrombosis and has relatively high affinity for endothelial (and possibly other) cells. Additionally, in a large multicenter clinical trial involving 3986 patients who had recovered from acute myocardial infarction, oral Sulodexide was associated with a 32% reduction in death and a significant reduction of left ventricular thrombus formation. Compared with heparin, low-Mr heparin, and unfractionated and low-Mr dermatan sulfates, the doses of Sulodexide required for antithrombotic efficacy suggest that the combination of heparin and dermatan sulfate in Sulodexide provides a more effective antithrombotic mechanism than heparin/low-Mr heparins (which catalyze the antiprotease actions of antithrombin III) or dermatan sulfate/low-Mr dermatan sulfate (which catalyze thrombin inhibition by heparin cofactor II).
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Canadian Red Cross Society, Blood Services and Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D001777:Blood Coagulation / Q000187:drug effects; D002341:Carotid Artery Thrombosis / Q000188:drug therapy; D002986:Clinical Trials as Topic; D003871:Dermatan Sulfate / Q000493:pharmacokinetics / Q000494:pharmacology; D004333:Drug Administration Routes; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006025:Glycosaminoglycans / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D015337:Multicenter Studies as Topic; D009203:Myocardial Infarction / Q000188:drug therapy; D010314:Partial Thromboplastin Time; D011817:Rabbits; D051381:Rats; D013927:Thrombosis / Q000188:drug therapy
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006025:Glycosaminoglycans; D003871:Dermatan Sulfate; C007858:glucuronyl glucosamine glycan sulfate; D006493:Heparin