PHARMACODYNAMICS OF A NEW LOW-MOLECULAR-WEIGHT DERMATAN SULFATE AFTER A SINGLE SUBCUTANEOUS INJECTION IN ELDERLY PATIENTS WITH CHRONIC VENOUS DISORDERS - A PHASE-I TRIAL

Fourteen patients, aged older than 65 years, with chronic venous disorders, underwent a Phase I pharmacodynamic study of the single subcutaneous (SC) administration of a new low-molecular-weight dermatan sulfate. Immediately before and 1, 2, 4, 6, 8, 12, and 24 hours after the SC injection of 100 mg of the drug, the following coagulation and fibrinolysis variables were checked: activated partial thromboplastin time, thrombin time, activated factor X (Xa) inhibition, global anticoagulant activity, as measured by Heptest, selected anti-IIa activity, as measured by Stachrom DS, functional and antigenic plasminogen-activator inhibitor, and functional tissue plasminogen activator. Routine laboratory blood and urine tests to monitor systemic tolerability of the drug were performed, The local tolerability and the occurrence of adverse events were also monitored. Results show anti-Xa and anti-IIa activity, as measured by Heptest and Stachrom DS, increased significantly after administration of the drug, thus suggesting an antithrombotic action. Functional and antigenic PAI concentrations were unchanged. Both systemic and local tolerability of a single SC dose of low-molecular-weight dermatan sulfate were very good.