Pharmacodynamic Effects of Sulodexide on Profibrinolytic and Haemorrheological Patterns

Abstract

Twenty-four patients with vascular disorders, randomly divided into 3 dosage groups of 8 patients, were treated with a single oral dose of sulodexide (50, 100 or 200mg) and placebo. Tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) activity and antigen, euglobulin lysis time, α2-antiplasmin, plasminogen, fibrinogen, blood and plasma viscosity, and whole blood filtration rate were determined before administration and over the following 24 hours. Sulodexide significantly increased t-PA activity linearly with the dose over the range of 50 to 200mg. At the same time, it also significantly decreased the concentration of PAI-1 linearly and proportionally with the dose. No clear effects were observed on the other monitored parameters, although euglobulin lysis time and plasma viscosity showed a tendency to decrease after the administration of sulodexide. These results justify the clinical activity of sulodexide. Indeed, the concomitant increase of t-PA and decrease of PAI-1 activity and antigen might increase the natural fibrinolytic activity with a physiological potentiation, without other adverse effects. The known activity of sulodexide in decreasing plasma viscosity during long term treatment is, however, not immediately explicable by the single-dose effects.

Sulodexide ameliorates early but not late kidney disease in models of radiation nephropathy and diabetic nephropathy

“…GAGs exert their antithrombotic action by accelerating the inhibition of activated serine proteases such as thrombin in the coagulation cascade by interacting with serine proteases inhibitors like antithrombin III and cofactor II [6][7][8][9]. Sulodexide can also promote fibrinolysis by increasing tissue plasminogen activator (tPA) activity and decreasing plasminogen activator inhibitor-1 (PAI-1) [10,11]. Sulodexide can also exert antilipemic effects promoting the release of lipoprotein lipase [12].…”

Treatment of venous leg ulcers with sulodexide

“…This antithrombotic activity in the arterial and venous vessels results from the inhibition activation of factor Xa and thrombin as well as inhibition of the thrombocytic agregation. Also, this drug activates the fibrinolytic system through the increase in plasminogen activity, the decrease of the plasminogen activity inhibitor and the decrease in blood viscosity (11,16,19).…”

Meta-Analysis of Some Results of Clinical Trials on Sulodexide Therapy in Peripheral Occlusive Arterial Disease

“…a ,9 .7D This decrease, together with that of triglycerides, explains the observed reduction in viscosity, as suggested previously. ":" Variations in plasma and serum viscosities are correlated strongly with the protein and lipoprotein composition of blood;" The antithrombotic action of sulodexide" could depend on the fibrinogen-lowering effect, on the inhibition of PAI-l, with concomitant increase oft-PA 73 and on the inhibition ofthe activation of Factor X. 74…”